RESUMEN
BACKGROUND: Athenaea fasciculata, a Brazilian native species from the Solanaceae family, is recognized as a promising source of bioactive withanolides, particularly Aurelianolide A and B, which exhibit significant antitumoral activities. Despite its potential, research on the chemical constituents of this species remains limited. This study aimed to dereplicate extracts and partitions of A. fasciculata to streamline the discovery of bioactive withanolides. METHODS: Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), various extracts-including n-hexane, methanol, and ethanol-were analyzed, and their mass spectrometry data were processed through the GNPS platform for the generation of molecular networking. The results indicated that crude extracts displayed comparable cytotoxicity against Jurkat cells, by treatment at 150 µg/mL, while alcoholic extracts achieved approximately 80% inhibition of K562 cells and K562-Lucena 1 at the same concentration. Notably, the dichloromethane partition exhibited the highest cytotoxicity across leukemia cell lines, particularly against Jurkat cells (IC50 = 14.34 µg/mL). A total of 22 compounds were annotated by manual inspection and different libraries, with six of them demonstrating significant cytotoxic effects. CONCLUSIONS: This research underscores the therapeutic potential of A. fasciculata and highlights the effectiveness of integrating advanced analytical methods in drug discovery, paving the way for further exploration of its bioactive compounds.
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Antineoplásicos Fitogénicos , Extractos Vegetales , Espectrometría de Masas en Tándem , Witanólidos , Humanos , Witanólidos/farmacología , Witanólidos/química , Witanólidos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células Jurkat , Solanaceae/química , Espectrometría de Masa por Ionización de Electrospray , Línea Celular Tumoral , Células K562RESUMEN
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.
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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 fármacosRESUMEN
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.
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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 , AnimalesRESUMEN
Cutaneous melanoma is an aggressive type of skin cancer that is recognized for its high metastatic potential and the challenges it presents in its treatment. There has been increasing interest in plant extracts and their potential applications in melanoma. The present study aimed to investigate the content of individual phenolic compounds in araçá-boi extract, evaluate their antioxidant activity, and explore their effects on cell viability, migration properties, oxidative stress levels, and protein expression in the human metastatic melanoma cell line SK-MEL-28. HPLC-DAD analysis identified 11 phenolic compounds in the araçá-boi extract. Trans-cinnamic acid was the main phenolic compound identified; therefore, it was used alone to verify its contribution to antitumor activities. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of araçá-boi extract and trans-cinnamic acid (200, 400, 600, 800, and 1600 µg/mL). Both the araçá-boi extract and trans-cinnamic acid reduced cell viability, cell migration, and oxidative stress in melanoma cells. Additionally, they modulate proteins involved in apoptosis and inflammation. These findings suggest the therapeutic potential of araçá-boi extract and its phenolic compounds in the context of melanoma, especially in strategies focused on preventing metastasis. Additional studies, such as the analysis of specific signaling pathways, would be valuable in confirming and expanding these observations.
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Movimiento Celular , Supervivencia Celular , Cinamatos , Melanoma , Fenoles , Extractos Vegetales , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/metabolismo , Movimiento Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Supervivencia Celular/efectos de los fármacos , Cinamatos/farmacología , Línea Celular Tumoral , Fenoles/farmacología , Antioxidantes/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.
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Antineoplásicos Fitogénicos , Proliferación Celular , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Aceites Volátiles , Neoplasias del Cuello Uterino , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Femenino , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Relación Estructura-Actividad , Estructura Molecular , Células Tumorales Cultivadas , Antineoplásicos/farmacología , Antineoplásicos/química , Células HeLaRESUMEN
AIM: To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). METHODS: Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. RESULTS: TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around -30 mV. CONCLUSION: Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.
Asunto(s)
Nanopartículas , Paclitaxel , Albúmina Sérica Humana , Paclitaxel/química , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Humanos , Nanopartículas/química , Albúmina Sérica Humana/química , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Fosfatos/química , Tampones (Química) , Concentración de Iones de Hidrógeno , Simulación del Acoplamiento Molecular , Liberación de FármacosRESUMEN
Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC.
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Apoptosis , Supervivencia Celular , Lepidium , Metanol , Extractos Vegetales , Proteína p53 Supresora de Tumor , Humanos , Células CACO-2 , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Supervivencia Celular/efectos de los fármacos , Metanol/química , Lepidium/química , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Fenoles/farmacología , Fenoles/químicaRESUMEN
Withanolides are steroidal lactones commonly found in plants of the Solanaceae family that have significant medicinal value. In this study, three withanolides extracted from Iochroma arborescens leaves were isolated and characterized. These included withaphysalin F (3: ) and two newly identified epimeric compounds: 18R- and 18S-O-methyl-withaphysalin F (1: and 2: ). Their structures were elucidated by NMR, IR, MS, CD, and X-ray diffraction analysis, and their potential against cell proliferation and migration was investigated. The cytotoxic assay revealed activity against different tumor and non-tumor cell lines. (18S)-O-methyl-withaphysalin F (2: ) presented cell death effects after at least 6 hours of exposure. MDA-MB-231 cells were exposed to 0.06 and 0.6 µM of (18S)-O-methyl-withaphysalin F (2: ), and reductions in cell adhesion, migration, and clonogenicity were observed. Morphological analysis revealed negative regulation in filopodia, salience, and roughness, as well as alterations in cellular microarchitecture. These results provide clues as to the effects of (18S)-O-methyl-withaphysalin F (2: ), allowing new molecular modifications to improve potency and selectivity and increase our antineoplastic arsenal.
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Antineoplásicos Fitogénicos , Movimiento Celular , Proliferación Celular , Humanos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Witanólidos/farmacología , Witanólidos/aislamiento & purificación , Witanólidos/química , Solanaceae/química , Estructura Molecular , Hojas de la Planta/químicaRESUMEN
Guatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α-gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O-methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O-methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively.
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Alcaloides , Aporfinas , Corteza de la Planta , Corteza de la Planta/química , Humanos , Aporfinas/farmacología , Aporfinas/química , Aporfinas/aislamiento & purificación , Línea Celular Tumoral , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Guatteria/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Supervivencia Celular/efectos de los fármacos , Estructura MolecularRESUMEN
Breast and gynecological cancers are major health concerns due to their increasing incidence rates, and in some cases, their low survival probability. In recent years, multiple compounds of natural origin have been analyzed as alternative treatments for this disease. For instance, Acetogenins are plant secondary metabolites from the Annonaceae family, and its potential anticancer activity has been reported against a wide range of cancer cells both in vitro and in vivo. Several studies have demonstrated promising results of Acetogenins' antitumor capacity, given their selective activity of cellular inhibition at low concentrations. This review outlines the origin, structure, and antineoplastic activities in vitro and in vivo of Acetogenins from Annonaceae against breast cancer and gynecological cancers reported to date. Here, we also provide a systematic summary of the activity and possible mechanisms of action of Acetogenins against these types of cancer and provide references for developing future therapies based on Acetogenins and nanotechnologies.
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Acetogeninas , Annonaceae , Antineoplásicos Fitogénicos , Neoplasias de la Mama , Neoplasias de los Genitales Femeninos , Acetogeninas/farmacología , Acetogeninas/química , Acetogeninas/aislamiento & purificación , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Annonaceae/química , Estructura Molecular , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , AnimalesRESUMEN
This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca2+-ATPase activity while inhibiting Na+, K+-ATPase activity in young and old rats. VCR altered the homeostasis of Mg2+-ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR's mechanistic pathways in aged rats, emphasizing the need for further research in this area.
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Adenosina Trifosfatasas , Envejecimiento , Estrés Oxidativo , Enfermedades del Sistema Nervioso Periférico , Ratas Wistar , Vincristina , Degeneración Walleriana , Animales , Vincristina/farmacología , Vincristina/toxicidad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Degeneración Walleriana/inducido químicamente , Degeneración Walleriana/patología , Degeneración Walleriana/metabolismo , Masculino , Envejecimiento/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07-1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26-100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.
Asunto(s)
Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Vincristina , Humanos , Vincristina/efectos adversos , Vincristina/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Niño , Femenino , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Preescolar , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Adolescente , Estudios Retrospectivos , Proteínas de Ciclo Celular/genética , Lactante , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Predisposición Genética a la Enfermedad , Genotipo , Alelos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Proteínas Asociadas a MicrotúbulosRESUMEN
Cancer prevails as one of the major health concerns worldwide due to the consistent rise in incidence and lack of effective therapies. Previous studies identified the peptides KLKKNL, MLKSKR, and KKYRVF from Salvia hispanica seeds and stated their selective anticancer activity. Thus, this study aimed to determine the cell death pathway induced by these peptides on five cancer cell lines (MCF-7, Caco2, HepG2, DU145, and HeLa). Based on the results of this work, it is possible to suggest that KLKKNL primarily induces selective cancer cell death through the apoptotic pathway in the Caco2 and HeLa lines. On the other hand, the peptide KKYRVF reported the highest statistical (p < 0.05) selective cytotoxic effect on the MCF-7, Caco2, HepG2, and DU145 cancer cell lines by induction of the necrotic pathway. These findings offer some understanding of the selective anticancer effect of KLKKNL, MLKSKR, and KKYRVF.
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Apoptosis , Péptidos , Salvia , Semillas , Humanos , Semillas/química , Péptidos/farmacología , Péptidos/química , Apoptosis/efectos de los fármacos , Salvia/química , Línea Celular Tumoral , Extractos Vegetales/farmacología , Extractos Vegetales/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Supervivencia Celular/efectos de los fármacos , Proteínas de Plantas/farmacología , Proteínas de Plantas/químicaRESUMEN
BACKGROUND: The leaves of Kalanchoe pinnata (Lam.) Pers. (K. pinnata), a succulent plant native to tropical regions, are used as a medicinal alternative against cancer in several countries worldwide; however, its therapeutic potential to fight cancer has been little addressed. In this study, we analyzed the phytochemical content, antioxidant capacity, and selectivity of K. pinnata leaf ethanolic extract against different human cancer cell lines in vitro. METHODOLOGY: This study subjected the ethanolic extract to enzymatic assays to quantify the phytochemical content (phenolics, flavonoids, and anthraquinones) and its radical scavenging and iron-reducing capacities. Also, the phytoconstituents and major phenolic compounds present in the extract's subfractions were identified by GC-MS, HPLC, and NMR. Human cancer (MCF-7, PC-3, HT-29) and normal colon (CoN) cell lines were treated with different concentrations of K. pinnata leaf ethanolic extract, and the changes in cell proliferation (sulforhodamine B assay), caspases activity (FITC-VAD-FMK reporter), mitochondrial membrane potential (MMP, rhodamine 123 assay), chromatin condensation/fragmentation (Hoechst 33342 stain), and ROS generation (DCFH2 probe assay) were assessed. RESULTS: The results showed that the K. pinnata leaf ethanolic extract is rich in phytoconstituents with therapeutic potential, including phenols (quercetin and kaempferol), flavonoids, fatty acid esters (34.6% of the total composition), 1- triacontanol and sterols (ergosterol and stigmasterol, 15.4% of the total composition); however, it presents a poor content of antioxidant molecules (IC50 = 27.6 mg/mL for H2O2 scavenging activity vs. 2.86 mg/mL in the case of Trolox). Notably, the extract inhibited cell proliferation and reduced MMP in all human cell lines tested but showed selectivity for HT-29 colon cancer cells compared to CoN normal cells (SI = 8.4). Furthermore, ROS generation, caspase activity, and chromatin condensation/fragmentation were augmented significantly in cancer-derived cell lines, indicating a selective cytotoxic effect. CONCLUSION: These findings reveal that the K. pinnata leaf ethanolic extract contains several bioactive molecules with therapeutic potential, capable of displaying selective cytotoxicity in different human cancer cell lines.
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Apoptosis , Kalanchoe , Extractos Vegetales , Hojas de la Planta , Especies Reactivas de Oxígeno , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Kalanchoe/química , Hojas de la Planta/química , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Antioxidantes/farmacologíaRESUMEN
BACKGROUND: The influences of Oxycodone (OXY) combined with Paclitaxel (PTX) on breast cancer cells are unclear. The present study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis, and migration of human breast cancer SKBR3 cells and the underlying mechanism. METHODS: The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. RESULTS: OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration, and invasion of SKBR3 cells as compared to the control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-â ¡, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with the control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. CONCLUSIONS: The present study indicates that OXY can enhance the antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.
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Apoptosis , Neoplasias de la Mama , Movimiento Celular , Proliferación Celular , Oxicodona , Paclitaxel , Humanos , Paclitaxel/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Línea Celular Tumoral , Oxicodona/farmacología , Movimiento Celular/efectos de los fármacos , Sinergismo Farmacológico , Supervivencia Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Reproducibilidad de los Resultados , Western BlottingRESUMEN
This work discusses the ongoing challenge of cancer, focusing on therapy issues such as chemotherapy resistance and adverse drug effects. It emphasizes the need for new anticancer agents with improved efficacy and fewer side effects, exploring natural products from plant sources. The Annonaceae family, specifically the Annona genus, is highlighted for its medicinal properties, including anti-inflammatory and anticancer effects. The study focuses on the isolation and elucidation of the substances present in Annona acutiflora leaves. The methodology involves chromatographic and spectroscopy techniques. The isolated compounds, (6S)-5'-oxohepten-1'E,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (1), (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (2) and (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (3) were investigated for cytotoxicity assays on cancer cell lines and normal cells. Results show promising cytotoxic activity, particularly with compound 3, demonstrating potential activity against oral cancer (43.18â µM), hepatocarcinoma (17.24â µM), melanoma (5.39â µM), and colon cancer (59.03â µM). The compound outperforms carboplatin in selectivity against oral cancer (S. I. 2.15) and melanoma (S. I. 17.22). The study concludes by suggesting the potential of these α-pyrones as effective and less toxic alternatives for cancer therapy.
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Annona , Antineoplásicos Fitogénicos , Ensayos de Selección de Medicamentos Antitumorales , Pironas , Humanos , Annona/química , Pironas/farmacología , Pironas/aislamiento & purificación , Pironas/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Hojas de la Planta/química , Relación Dosis-Respuesta a Droga , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificaciónRESUMEN
It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.
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Antiinflamatorios , Antioxidantes , Lantana , Extractos Vegetales , Humanos , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Lantana/química , Antiinflamatorios/farmacología , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for modifying complex natural products, leading to analogs that are unattainable by chemical semisynthesis or total synthesis. In this report, through the combination of natural products chemistry and diversity-oriented synthesis, a diversity-enhanced extracts approach is proposed using chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. This method was applied to subextract enriched in sesquiterpene lactones from Ambrosia tenuifolia (Fam. Asteraceae) using acid media conditions (p-toluenesulfonic acid) to change molecular skeletons. The chemically modified extract was then fractionated by a bioguided approach to obtain the pure compounds responsible for the anti-glioblastoma (GBM) activity in T98G cell cultures. Indeed, with the best candidate, chronobiological experiments were performed to evaluate temporal susceptibility to the treatment on GBM cell cultures to define the best time to apply the therapy. Finally, bioinformatics tools were used to supply qualitative and quantitative information on the physicochemical properties, chemical space, and structural similarity of the compound library obtained. As a result, natural products derivatives containing new molecular skeletons were obtained, with possible applications as chemotherapeutic agents against human GBM T98G cell cultures.
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Glioblastoma , Extractos Vegetales , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Línea Celular Tumoral , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Productos Biológicos/química , Productos Biológicos/farmacología , Asteraceae/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Lactonas/química , Lactonas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Baccharis macraei Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress in plant species, against which they present defensive mechanisms. For this reason, the objective was to evaluate the effect of abiotic stress generated by the proximity of B. macraei to the industrial complex by assessing the physiological and metabolic states reported by the extracts and compounds isolated from the species, as well as the photosynthetic capacity, metal content and production, and antioxidant activity and cytotoxicity against tumorigenic cell lines of the phytoconstituents. To this end, B. macraei was collected at two different distances from the industrial complex, observing that the closer the species is, the greater the concentration of copper in the soil, generating a decrease in the rate of electron transport in situ, but an increase in antioxidant activity with low cytotoxicity. This activity could be due to the presence of flavonoids such as Hispidulin, Cirsimaritina, and Isokaempferida, as well as monoterpenes, oxygenated and non-oxygenated sesquiterpenes identified in this study.
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Antioxidantes , Baccharis , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Baccharis/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Línea Celular Tumoral , Chile , Fotosíntesis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificaciónRESUMEN
Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO2 after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO2 were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 µg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.