Asunto(s)

Neoplasias , Fitoquímicos , Humanos , Fitoquímicos/farmacología , Fitoquímicos/química , Fitoquímicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química

RESUMEN

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.

Asunto(s)

Neoplasias de la Mama , Ácido Hialurónico , Hidrogeles , Paclitaxel , Terapia Fototérmica , Animales , Ácido Hialurónico/química , Hidrogeles/química , Hidrogeles/farmacología , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ratones , Terapia Fototérmica/métodos , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/administración & dosificación , Humanos , Indoles/química , Indoles/farmacología , Ratones Endogámicos BALB C , Polímeros/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fototerapia/métodos

RESUMEN

To explore new compounds with antitumour activity, fifteen phenolic nor-tripterpenes isolated from Celastraceae species, Maytenus jelskii, Maytenus cuzcoina, and Celastrus vulcanicola, have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI50 ranging from 0.45 to 8.6 µM) on at least five of the cell lines tested. Continuous live cell imaging identified apoptosis as the mode of action of selective cell killing in HeLa cells. Furthermore, their effect on a drug-sensitive Saccharomyces cerevisiae strain has been investigated to deepen on their mechanism of action. In dose-response growth curves, zeylasteral and 7α-hydroxy-blepharodol were markedly active. Additionally, halo assays were conducted to assess the involvement of oxidative stress and/or mitochondrial function in the anticancer profile, ruling out these modes of action for the active compounds. Finally, we also delve into the structure-activity relationship, providing insights into how the molecular structure of these compounds influences their biological activity. This comprehensive analysis enhances our understanding of the therapeutic potential of this triterpene type and underscores its relevance for further research in this field.

Asunto(s)

Antineoplásicos Fitogénicos , Apoptosis , Humanos , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Fenoles/farmacología , Fenoles/química , Triterpenos/farmacología , Triterpenos/química , Células HeLa , Celastraceae/química , Línea Celular Tumoral , Extractos Vegetales/farmacología , Extractos Vegetales/química , Saccharomyces cerevisiae/efectos de los fármacos , Células A549 , Estructura Molecular , Proliferación Celular/efectos de los fármacos

RESUMEN

The cell signaling pathways involved in the antiproliferative activities of T. rosea inner bark remain unexplored. This study evaluated the apoptotic effects of two iridoids from the inner bark of T. rosea and apicidin on THP-1 cells. The cytotoxic effects of the extract and the pure compounds on THP-1 and Jurkat cells were also evaluated using the MTT assay. The apoptotic effect was determined by measuring the mitochondrial membrane potential. The expression of mRNA and MAPK kinase, Bax, and Bcl-2 proteins was detected by Western blotting and RT-qPCR, respectively. The extract and the compounds evaluated increased the percentage of apoptotic cells. Depolarization of the mitochondrial membrane was observed, and the number of cells in the G0/G1 phase increased. Catalposide and specioside significantly increased p38 protein expression, mostly in cells pretreated with apicidin. The p38 MAPK signaling pathway is at least one of the pathways by which the n-butanol extract obtained from Tabebuia rosea, catalposide, and specioside exerts its apoptotic effect on THP-1 cells, and this effect generates a response in the G0/G1 phase and subsequent cell death. In addition, there was depolarization of the mitochondrial membrane, an effect that was related to the participation of the proapoptotic protein Bax.

Asunto(s)

Apoptosis , Potencial de la Membrana Mitocondrial , Corteza de la Planta , Extractos Vegetales , Tabebuia , Humanos , Apoptosis/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Corteza de la Planta/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Tabebuia/química , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Células Jurkat , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Leucemia/patología , 1-Butanol/química , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Células THP-1 , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos

RESUMEN

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions.

Asunto(s)

Antineoplásicos Fitogénicos , Neoplasias , Extractos Vegetales , Scutellaria , Scutellaria/química , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Neoplasias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Proliferación Celular/efectos de los fármacos

RESUMEN

Sangre de drago, the sap of Croton lechleri Müll. Arg. tree, has been used for centuries in traditional medicine owing to its diverse biological activities. Extracts derived from different parts of the species contain a multitude of phytochemicals with varied applications. Twigs, however, are among the least studied parts of the plant. This study unveils new biological activities of Croton lechleri twig extracts recovered by applying Soxhlet and advanced green techniques. For all extracts, total phenolic content and antioxidant activity were determined. Subsequently, four were selected, and their cytotoxic effects were assessed on both normal (HaCat) and malignant melanoma (A375) skin cell lines using the MTT assay and trypan blue exclusion assay. All showed dose-dependent cytotoxicity, with the Soxhlet ethanol extract demonstrating the highest selectivity towards A375 cells over HaCat cells. The extracts induced apoptosis and necrosis, as confirmed by Annexin V/PI dual-labeling and flow cytometry, highlighting their ability to trigger programmed cell death in cancer cells. The selective inhibition of cell cycle progression in A375 compared to HaCat observed both for Soxhlet ethanol and pressurized ethanol extracts induces cell cycle arrest at multiple points, primarily in the G1 and G2/M phases, and significantly reduces DNA synthesis as evidenced by the decrease in the S-phase population, confirmed by the EdU assay. Consequently, the Soxhlet extract composition was analyzed using LC-MS, which revealed their richness in polyphenolic compounds, particularly flavonoids from the flavonol subclass.

Asunto(s)

Antioxidantes , Apoptosis , Croton , Extractos Vegetales , Croton/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Antioxidantes/farmacología , Antioxidantes/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/química , Supervivencia Celular/efectos de los fármacos , Fenoles/farmacología , Fenoles/química

RESUMEN

The emergence of natural products has provided extremely valuable references for the treatment of various diseases. Cucurbitacin B, a tetracyclic triterpenoid compound isolated from cucurbitaceae and other plants, is the most abundant member of the cucurbitin family and exhibits a wide range of biological activities, including anti-inflammatory, anti-cancer, and even agricultural applications. Due to its high toxicity and narrow therapeutic window, structural modification and dosage form development are necessary to address these issues with cucurbitacin B. This paper reviews recent research progress in the pharmacological action, structural modification, and application of cucurbitacin B. This review aims to enhance understanding of advancements in this field and provide constructive suggestions for further research on cucurbitacin B.

Asunto(s)

Triterpenos , Triterpenos/química , Triterpenos/farmacología , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Animales , Cucurbitaceae/química , Estructura Molecular , Relación Estructura-Actividad , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología

RESUMEN

Elephantopus tomentosus (ET) Linn. was reported to be an anti-tumor plant. However, the chemical composition of ET and its anti-tumor compounds and potential mechanisms still unclear. In this paper, UPLC-Q-TOF-MS/MS was firstly used to identified the ingredients in ET and UPLC was used to determine the main compounds of ET. Network pharmacology was applied to predict the potential mechanisms of anti-liver cancer. Anti-tumor nuclear activate compounds and targets of ET were obtained and the anti-liver cancer effect was validated on HepG2. Finally, Molecule docking, RT-qPCR, and western blotting were used for verification of the relationship between nuclear activate compounds and nuclear targets and the potential anti-cancer mechanisms. The result showed that 42 compounds were identified in ET, which consisted of sesquiterpene lactones, flavonoids, and phenylpropanoid compounds. Scabertopin (ST), chlorogenic acid, Isochlorogenic acid B, Isochlorogenic acid A and Isochlorogenic acid C were identified as main compounds and were determined as 0.426%, 0.457%, 0.159%, 0.701%, and 0.103% respectively. 24 compounds showed high pharmacokinetics and good drug-likeness. 520 overlapping targets of the ET compounds and liver cancer were collected. The targets were used for KEGG and GO analysis. GO enrichment analysis suggested that the targets of 24 active compound closed related to promote apoptosis, inhibit proliferation, and regulate oxidative levels. KEGG enrichment analysis suggested that pathway in cancer was enriched most and p38 MAPK/p53 signaling pathway, which closely related to promoting apoptosis and inhibiting proliferation. Compounds-targets analysis based on the parameter of Betweenness, Closeness, Information, Eigenvector, Degree, and component content indicated that ST was the nucleus anti-tumor active compound of ET. HepG2 was first used to validated the anti-tumor effect of ST and the result showed that ST significantly inhibited HepG2 proliferation with a low IC50 less than 5 µM. Nucleus active compound targets, including TP53, CASP3, BCL2, EGFR, TNF-a, IL-1ß, and IL-6 were enriched based on degree value of PPI analysis. Molecule docking suggested that ST showed a good combination to TGFBR1 with the combination energy less than - 5 kcal/mol. RT-qPCR result also suggested that ST significantly medicated the mRNA expression level of TP53, CASP3, BCL2, EGFR, TNF-a, IL-1ß, and IL-6. Protein expression of p-p38/p38 and p-p53/p53 notable increased by ST treatment. In conclude, combining with UPLC-Q-TOF-MS/MS qualitative analysis, UPLC quantitative analysis, network pharmacology analysis, molecule docking, and in vitro experiments on HepG2, we suggest that ST is an anti-tumor ingredient of ET, which may target to TGFBR1 and promote apoptosis and inhibited proliferation of HepG2 by activating p38 MAPK/p53 signaling pathway. ST can be regarded as a quality marker of ET.

Asunto(s)

Neoplasias Hepáticas , Simulación del Acoplamiento Molecular , Humanos , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Asteraceae/química , Simulación por Computador , Espectrometría de Masas en Tándem , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos

RESUMEN

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography-mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 µg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph-mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties.

Asunto(s)

Antineoplásicos Fitogénicos , Hyptis , Extractos Vegetales , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Línea Celular Tumoral , Hyptis/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Cromatografía de Gases y Espectrometría de Masas , Metaboloma , Metabolómica/métodos , Cromatografía Líquida de Alta Presión , Supervivencia Celular/efectos de los fármacos

RESUMEN

Chinese Olea europaea leaves, rich in verbascosides, were extracted using ultrasound-assisted extraction (UAE) and wall-breaking extraction (WBE) with deep eutectic solvents (Optimal UAE: 55 min, 200 mL/g liquid-solid ratio, 20% moisture, yielding 206.23 ± 0.58 mg GAE/g total phenolic content (TPC) and 1.59 ± 0.04% verbascoside yield (VAY); Optimal WBE: 140 s, 210 mL/g, 30% moisture, giving 210.69 ± 0.97 mg GAE/g TPC and 1.33 ± 0.2% VAY). HPLC analysis showed that young leaves accumulated higher TPC and phenolic compounds. Among the five olive varieties, Koroneiki and Chemlal showed the highest TPC in UAE, while Arbosana and Chemlal excelled in WBE. WBE yielded a higher TPC and rutin, whereas UAE marginally increased other phenolics. Additionally, the DPPH• assay showed that WBE-extracted verbascoside-rich extracts (VREs) of Chemlal exhibited high antioxidant activity (EC50 of 57 mg/mL), but Koroneiki-VREs exhibited lower activity against the ABTS•+ radical (EC50 of 134 mg/mL). Remarkably, the UAE/WBE-extracted Chemlal-VREs promoted the normal esophageal Het-1A cell line at 25 µg/mL for 24 h; yet, the esophageal cancer Eca-109 cells were sensibly inhibited, especially at 50 µg/mL; and the cell viability decreased dramatically. The results confirmed WBE as a relatively efficient method, and the Chemlal variety may be an excellent source of verbascoside.

Asunto(s)

Antioxidantes , Glucósidos , Olea , Fenoles , Extractos Vegetales , Hojas de la Planta , Solventes , Olea/química , Hojas de la Planta/química , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Glucósidos/aislamiento & purificación , Glucósidos/química , Glucósidos/farmacología , Solventes/química , Humanos , Línea Celular Tumoral , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cromatografía Líquida de Alta Presión , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Pueblos del Este de Asia , Polifenoles

RESUMEN

Olive trees not only produce olives but also generate a substantial amount of waste and by-products, including leaves, pomace (the solid remains after pressing olives for oil), and wastewater from the olive oil-making process. The waste products, particularly the leaves, contain bioactive compounds, especially phenolic compounds, known for their health benefits, such as high antioxidant potential and the ability to reduce inflammation. These compounds have shown promise in preventing and treating cancer. This review, based on in vitro evidence, provides a detailed description and discussion of the mechanisms through which these compounds from olive leaves can prevent development, the ways they might act against cancer cells, and their potential to increase the sensitivity of tumor cells to conventional anticancer therapy. The possible synergistic effects of these compounds suggest that olive leaf extracts may offer a promising approach for cancer treatment, compared with isolated compounds, thus providing novel possibilities for cancer therapy.

Asunto(s)

Olea , Extractos Vegetales , Hojas de la Planta , Olea/química , Hojas de la Planta/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antioxidantes/farmacología , Antioxidantes/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Fenoles/farmacología , Fenoles/química , Antineoplásicos/farmacología , Antineoplásicos/química , Animales

RESUMEN

The Jurassic relict Royal fern, Osmunda regalis L., is widely distributed across temperate zones in the Northern and Southern hemispheres. Even though this species has been utilised for centuries as a medicinal plant, its phytochemical composition mainly remains unknown. As part of our ongoing research to identify potential lead compounds for future anticancer drugs, 17 natural products were characterised from the aerial parts of Osmunda regalis L. Fifteen of these compounds were identified in this species for the first time, including the six previously undescribed compounds kaempferol 3-O-(2''-O-(2'''-α-rhamnopyranosyl)-ß-glucopyranosyl)-ß-glucopyranoside, quercetin 3-O-(2''-O-(2'''-α-rhamnopyranosyl)-ß-glucopyranosyl)-ß-glucopyranoside, kaempferol 3-O-(2''-O-(2'''-α-rhamnopyranosyl-6'''-O-(E)-caffeoyl-)-ß-glucopyranosyl)-ß-glucopyranoside, 3-methoxy-5-hydroxy-4-olide, 4-hydroxy-3-(3'-hydroxy-4'-(hydroxyethyl)-oxotetrafuranone-5-methyl tetrahydropyranone, and 4-O-(5-hydroxy-4-oxohexanoyl) osmundalactone. The molecular structures were determined by combining several 1D and 2D NMR experiments, circular dichroism spectroscopy, and HRMS. Determination of cytotoxicity against AML MOLM-13, H9c2, and NRK cell lines showed that two isolated lactones exhibited significant cytotoxic activity.

Asunto(s)

Productos Biológicos , Productos Biológicos/química , Productos Biológicos/farmacología , Humanos , Helechos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Espectroscopía de Resonancia Magnética

RESUMEN

Lepidagathis cristata (L. cristata) plant produces reducing and capping agents; this study utilized microwave-assisted biogenic synthesis to manufacture silver nanoparticles (AgNPs) using this plant. The structure, morphology, and crystallinity phases of prepared nanoparticles (NPs) were characterized by ultraviolet-visible spectroscopy (UV-viz), powder X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). Biologically synthesized AgNPs were treated against pathogenic bacteria species including Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), and Staphylococcus aureus (S. aureus) and its highest zone of inhibition 10 ± 1.45 mm, 10 ± 0.74 mm, and 6 ± 0.43 mm, respectively, at the concentration of 100 µg/mL. The cytotoxic activity of AgNPs against MCF-7 breast cancer cells revealed significant growth inhibition by inhibiting cell viability, inhibitory concentration of 50% (IC50) of NPs observed at 55.76 µg/mL concentration. Finally, our findings concluded that the L. cristata-mediated biosynthesized AgNPs proved its potential antibacterial and neoplastic properties against MCF cells by endorsing the inhibition of cell proliferation especially with low concentration.

Asunto(s)

Antibacterianos , Ensayos de Selección de Medicamentos Antitumorales , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Plata , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Humanos , Células MCF-7 , Extractos Vegetales/química , Extractos Vegetales/farmacología , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Staphylococcus aureus/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/síntesis química , Agua/química , Relación Dosis-Respuesta a Droga , Femenino

RESUMEN

Liver cancer is the third leading cause of cancer deaths globally. The use of Hydroxycamptothecin (HCPT) as a first-line chemotherapeutic agent for liver, lung, and gastric cancers is often hampered by its low activity, limited targeting, and poor water solubility. This results in a low accumulation of HCPT in tumor cells, as well as the inability to maintain continuous treatment. Consequently, there is an urgent need to develop an accessory method that can enhance the therapeutic efficacy of HCPT while exhibiting good biocompatibility and targeted delivery ability. To address this critical issue, an enzyme-triggered supramolecular nanocarrier, refer as SCD/LCC SNCs, has been successfully developed, leveraging the aggregation of the negatively charged sulfate-modified ß-CDs and positively charged lauroylcholine chloride (LCC). This nanocarrier demonstrates acetylcholinesterase (LCC) triggered decomposition behavior, making it a promising drug carrier for HCPT. The cellular assays conducted have demonstrated that HCPT loaded into these SCD/LCC SNCs exhibit reduced cytotoxicity towards normal cells while maintaining robust tumor inhibitory activity and inducing apoptosis. Therefore, this study offers a promising strategy for the effective use of HCPT in the treatment of liver cancer.

Asunto(s)

Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Camptotecina/farmacología , Camptotecina/química , Camptotecina/análogos & derivados , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/química , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Células Hep G2

RESUMEN

The current research was conducted to explore, for the first time, Tagetes erecta L. (family Asteraceae) fruits from northwest Iran in terms of the chemical composition of essential and fixed oils, their cytotoxic activities, and the inhibitory effect of essential oil on the PI3K/AKT/mTOR signaling pathway. The volatile oil was obtained through hydrodistillation (Clevenger apparatus). According to gas chromatography-mass spectrometry analysis, the essential oil was rich in cyclic monoterpenoids, 2-isopropyl-5-methyl-3-cyclohexen-1-one (19.99%), D-limonene (12.75%), terpinolene (11.64%) and also the saturated fatty acid palmitic acid (19.09%). Furthermore, the seeds of T. erecta were extracted using hexane by the maceration method. The analysis of fatty acid profile of the fixed oil by gas chromatography-flame ionization detector (GC-FID) demonstrated that the most predominant fatty acids in fixed oil were linoleic acid (59.53%), palmitic acid (13.70%), stearic acid (10.20%), and oleic acid (9.20%). The cytotoxic activity of essential oil, crude oil, and fraction A (obtained from fixed oil) were evaluated by using the MTT assay on MCF7 (human breast cancer cell line), PC3 (human prostate cancer cell line), and U87MG (human glioblastoma cell line). Finally, the effect of essential oil on inhibiting the PI3K/Akt/mTOR signaling pathway was evaluated using real-time PCR. The essential oil exhibited vigorous cytotoxic activity on the U87MG cell line, with an IC50 value of 32.65 µg/mL. Interestingly, the essential oil significantly inhibited the PI3K/AKT/mTOR cascade compared to the non-treated group. Our results suggest that the essential oil holds promise as an anticancer agent for glioblastoma cell lines. To the best of our knowledge, this study is the first to report on the profile of the essential oil of T. erecta fruits and its implications for targeting the PI3K/AKT/mTOR signaling pathway.

Asunto(s)

Frutas , Aceites Volátiles , Transducción de Señal , Tagetes , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/química , Transducción de Señal/efectos de los fármacos , Tagetes/química , Frutas/química , Línea Celular Tumoral , Irán , Proteínas Proto-Oncogénicas c-akt/metabolismo , Aceites de Plantas/farmacología , Aceites de Plantas/química , Serina-Treonina Quinasas TOR/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Fosfatidilinositol 3-Quinasas/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Proliferación Celular/efectos de los fármacos

RESUMEN

OBJECTIVE: Preparation and characterization of nano-emulsion formulations for Asparagus densiflorus aerial and root parts extracts. SIGNIFICANCE: Genus Asparagus is known for its antimicrobial and anticancer activities, however, freeze dried powder of aqueous - alcoholic extract prepared in this study, exhibited a limited water solubility, limiting its therapeutic application. Thus, encapsulation of its phytochemicals into nano-emulsion is proposed as a solution to improve water solubility, and facilitate its clinical translation. METHODS: the composition of extracts for both aerial and root parts of Asparagus densiflorus was identified by HPLC and LC-MS analysis. Nano-emulsion was prepared via homogenization where a mixture of Castor oil: phosphate buffered saline (10 mM, pH 7.4): Tween 80: PEG 600 in a ratio of 10: 5: 2.5: 2.5, respectively. Nano-emulsion formulations were characterized for particle size, polydispersity index (PDI), zeta potential, TEM, viscosity and pH. Then, the antibacterial and anticancer activities of nano-emulsion formulations versus their pure plant counterparts was assessed. RESULTS: The analysis of extracts identified several flavonoids, phenolics, and saponins which were reported to have antimicrobial and anticancer activities. Nano-emulsion formulations were monodispersed with droplet sizes ranging from 80.27 ± 2.05 to 111.16 ± 1.97 nm, and polydispersity index ≤0.3. Nano-emulsion formulations enhanced significantly the antibacterial (multidrug resistant bacteria causing skin and dental soft tissues infections) and anticancer (HuH7, HEPG2, H460 and HCT116) activities compared to their pure plant extract counterparts. CONCLUSION: Employing a nano-delivery system as a carrier for phytochemicals might be an effective strategy to enhance their pharmacological activity, overcome their limitations, and ultimately increase their potential for clinical applications.

Asunto(s)

Antibacterianos , Asparagus , Emulsiones , Componentes Aéreos de las Plantas , Extractos Vegetales , Raíces de Plantas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Componentes Aéreos de las Plantas/química , Asparagus/química , Raíces de Plantas/química , Tamaño de la Partícula , Nanopartículas/química , Pruebas de Sensibilidad Microbiana , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Solubilidad , Línea Celular Tumoral , Composición de Medicamentos/métodos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación

RESUMEN

Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. Results: Through a comprehensive literature review and the Integrated Medicinal Plant Phytochemistry and Therapeutics database (IMPPAT), we identified 33 bioactive molecules from P. longum. Subsequent analyses employing tools such as SwissTargetPrediction, SuperPred, and DIGEP-Pred facilitated the isolation of 676 potential targets, among which 72 intersected with 666 lung cancer-associated genetic markers identified through databases including the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards. Further validation through protein-protein interaction (PPI) networks, gene ontology, pathway analyses, boxplots, and overall survival metrics underscored the therapeutic potential of compounds such as 7-epi-eudesm-4(15)-ene-1ß, demethoxypiplartine, methyl 3,4,5-trimethoxycinnamate, 6-alpha-diol, and aristolodione. Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics.

Asunto(s)

Neoplasias Pulmonares , Simulación del Acoplamiento Molecular , Farmacología en Red , Piper , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Piper/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/química , Mapas de Interacción de Proteínas/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/química , Plantas Medicinales/química

RESUMEN

The genus Allium plants, including onions, garlic, leeks, chives, and shallots, have long been recognized for their potential health benefits, particularly in oxidative and cancer prevention. Among them, onions and garlic have been extensively studied, unveiling promising biological activities that are indicative of their potential as potent antioxidant and anticancer agents. Research has revealed a rich repository of bioactive compounds in Allium species, highlighting their antioxidative properties and diverse mechanisms that target cancer cells. Compounds such as allicin, flavonoids, and organosulfur compounds (OSCs) exhibit notable antioxidant and anticancer properties, affecting apoptosis induction, cell cycle arrest, and the inhibition of tumor proliferation. Moreover, their antioxidant and anti-inflammatory attributes enhance their potential in cancer therapy. Studies exploring other Allium species beyond onions and garlic have revealed similar biological activities, suggesting a broad spectrum of natural products that could serve as promising candidates for developing novel anticancer treatments. Understanding the multifaceted potential of Allium plants will pave the way for innovative strategies in oxidative and cancer treatment and prevention, offering new avenues for pharmaceutical research and dietary interventions. Therefore, in this review, we compile an extensive analysis of the diversity of various Allium species, emphasizing their remarkable potential as effective agents.

Asunto(s)

Allium , Antioxidantes , Allium/química , Humanos , Antioxidantes/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos

RESUMEN

Styphnolobium japonicum leaves are considered a rich source of flavonoids, which are the prospective basis for various therapeutic effects. However, there has been a lack of comprehensive cytotoxic studies conducted on these leaves. Therefore, this ongoing investigation aimed to detect and isolate the flavonoids present in S. japonicum leaves, and assess their antioxidant and anticancer properties. The defatted extract from S. japonicum leaves was analyzed using HPLC, which resulted in the identification of seven phenolics and six flavonoids. Rutin and quercetin were found to be the most abundant. Furthermore, a comprehensive profile of flavonoids was obtained through UPLC/ESI-MS analysis in negative acquisition mode. Fragmentation pathways of the identified flavonoids were elucidated to gain relevant insights into their structural characteristics. Furthermore, genistein 7-O-glucoside, quercetin 3-O-rutinoside, and kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 6)-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranoside were isolated and characterized. The defatted extract rich in flavonoids exhibited significant antioxidant, iron-reducing, free radicals scavenging impacts, and remarkable cytotoxicity against the liver cell line (IC50 337.9µg/ mL) and lung cell line (IC50 55.0 µg/mL). Furthermore, the antioxidant and anticancer capacities of the three isolated flavonoids have been evaluated, and it has been observed that their effects are concentration-dependent. The findings of this research highlight the promising impact of flavonoids in cancer therapy. It is recommended that future scientific investigations prioritize the exploration of the distinct protective and therapeutic characteristics of S. japonicum leaves, which hold significant potential as a valuable natural resource.

Asunto(s)

Antioxidantes , Flavonoides , Extractos Vegetales , Hojas de la Planta , Hojas de la Planta/química , Flavonoides/farmacología , Flavonoides/química , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Egipto , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Quercetina/farmacología , Quercetina/análogos & derivados , Quercetina/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Fenoles/farmacología , Fenoles/química , Rutina/farmacología , Rutina/química , Sophora japonica

RESUMEN

Utilizing medicinal plants and other natural resources to prevent different types of human cancers is the prime focus of attention. Cervical cancer in women ranks as the fourth most common type of malignancy. The current study used gas chromatography-mass spectrometry (GC-MS) to identify the active phytochemical constituents from Caladium lindenii leaf extracts using ethanol (ECL) and n-hexane (HCL) solvents. Plant extracts were tested for potential cytotoxic effects on HeLa and HEK-293 T cells using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and the crystal violet assays. SYBR Green-based real-time PCR was performed to assess the mRNA expression profile of the apoptosis biomarkers (BCL-2 and TP53). The molecular interaction of the compounds with the targeted proteins (TP53, BCL2, EGFR, and HER2) was determined using molecular docking. GC-MS analysis revealed a total of 93 compounds in both extracts. The ECL extract significantly reduced the proliferation of HeLa cervical cancer cells, with an IC50 value of 40 µg/mL, while HEK-293 T cells showed less effect (IC50 = 226 µg/mL). The quantitative RT-PCR gene expression analysis demonstrated the ethanol extract regulated TP53 and BCL2 mRNA expressions in treated cancer cell samples. Heptanediamide, N,N'-di-benzoyloxy-(- 10.1) is the best-docked ligand with a TP53 target found in the molecular docking study, whereas EGFR/Clionasterol had the second highest binding affinity (- 9.7), followed by EGFR/Cycloeucalenol (- 9.6). It is concluded that ECL extract has promising anti-cervical cancer potential and might be valued for developing new plant-derived anticancer agents after further investigations.

Asunto(s)

Apoptosis , Cromatografía de Gases y Espectrometría de Masas , Simulación del Acoplamiento Molecular , Extractos Vegetales , Neoplasias del Cuello Uterino , Humanos , Células HeLa , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Células HEK293 , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética