RESUMEN

BACKGROUND: Despite remarkable advances, cancer has remained the second cause of death, which shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of treating diseases, and several approved chemotherapeutic compounds were isolated from plants. OBJECTIVE: The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian, breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production. METHODS: Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS. RESULTS: Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively in A2780CP cells after 30 minutes and up to 24 hours. CONCLUSION: Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells. Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic studies.

Asunto(s)

Antineoplásicos Fitogénicos , Apoptosis , Neoplasias de la Mama , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma , Neoplasias Ováricas , Extractos Vegetales , Raíces de Plantas , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Apoptosis/efectos de los fármacos , Femenino , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Células Tumorales Cultivadas , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Aim To study the antitumor effect of cispl-atin ( DDP) chemotherapy promoted by Taohong Siwu Decoction (TSD) on mice with lung adenocarcinoma mice. Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma trans¬plantation mouse model. Normal control, Model, TSD, DDP, TSD + DDP groups were set up. The change of transplanted tumor volume after administration was observed, the weight of transplanted tumor was weighed, the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry, TUNEL was detected by fluorescence staining, Bcl-2, Bax, cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting, and the content of D-dirtier in plasma was measured by ELISA. Results DDP plus TSD significantly inhibited the growth of transplanted tumor. Ki67 expression in tumor tissue was lower than that in DDP group (28. 3% ±3. 1% vs 40. 3% ±2.1% ). The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor. The positive rate of TUNEL was significantly higher than that of DDP group (41. 0% ±3.0% vs 30.7% ± 4.5%). Bax, cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group, while the expression of Bcl-2 was significantly lower than that of DDP group. Moreover, we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins ( P < 0.05 ) . The plasma D-dimer content in TSD + DDP group was significantly lower than that in DDP group (188. 50 ± 28. 46 vs 269.80 ± 35.92) μg • L

RESUMEN

BACKGROUND: One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis, ulcerative colitis and ankylosing spondylitis. OBJECTIVE: Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity. METHOD: Renal toxicity was caused by administration of single cisplatin injection at 22 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments. RESULTS: Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and ß-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1ß, MCP-1, ICAM-1, and TGF-ß1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1ß, ICAM-1, and TGF-ß1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice. CONCLUSION: The study's results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.

Asunto(s)

Cisplatino , Interleucina-10 , Animales , Anticuerpos Monoclonales , Apoptosis , Cisplatino/efectos adversos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Riñón , Ratones , Estrés Oxidativo , Factor de Crecimiento Transformador beta1/metabolismo , Inhibidores del Factor de Necrosis Tumoral

RESUMEN

Drug delivery systems with controlled release have been considered important tools for the treatment of various diseases. The efficacy of the drug can be enhanced by increasing its solubility, stability, bioavailability, and specific site delivery. Herein, we investigated cisplatin (cisP) loading efficacy and release potentiality on chitosan (CS) functionalized with magnetite (M), silicon dioxide (S), and graphene oxide (GO) nanoparticles. Different nanocomposites [chitosan-coated magnetite, silicon dioxide, and graphene oxide (CS/M/S/GO); chitosan-coated magnetite and silicon dioxide (CS/M/S); chitosan-coated silicon dioxide (CS/S); and chitosan-coated magnetite (CS/M)] were prepared. The prepared nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy, transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). DFT calculations were employed to explore the interaction mechanism of cisP with a selected chitosan-functionalized nanocomposite in the gas phase and water media. The UV-Vis spectroscopy was used to study cisP loading and release from the prepared nanocomposites. The results showed that the highest loading efficacy was achieved by CS/M and CS/M/S/GO nanocomposites (87% and 84% respectively). While the releasing potentiality for CS/M composite was the highest compared with the other ones (91%).

Asunto(s)

Quitosano/química , Portadores de Fármacos/química , Óxido Ferrosoférrico/química , Grafito/química , Nanocompuestos/química , Dióxido de Silicio/química , Cisplatino/metabolismo , Liberación de Fármacos

RESUMEN

TIPE2 participates in multiple types of cancer development. However, its mechanism underlying chemoresistance in osteosarcoma has not been elucidated. Herein, we observed the expression of TIPE2 and MDR1 in cis-platin-resistant osteosarcoma tissues and cell lines. Compared to their matched sensitive cell lines and tissues, TIPE2 was downregulated while MDR1 expression was increased. Further investigation showed that overexpression of TIPE2 effectively inhibited MDR1 expression and greatly sensitized osteosarcoma cells to cis-platin, both in vivo and in vitro. Mechanistically, TIPE2 inhibited the transcription of the MDR1 promoter by interfering with the TAK1-NF-κB and -AP-1 pathways. Overall, our results elucidated for the first time that TIPE2 sensitizes osteosarcoma cells to cis-platin through downregulation of MDR1 and may be a novel target in osteosarcoma therapy.

Asunto(s)

Cisplatino/farmacología , Regulación hacia Abajo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , FN-kappa B/metabolismo , Osteosarcoma/metabolismo , Factor de Transcripción AP-1/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Osteosarcoma/patología , Transducción de Señal/efectos de los fármacos , Transcripción Genética/efectos de los fármacos

RESUMEN

In normal and cancer cells, successful cell division requires accurate duplication of chromosomal DNA. All cells require a multiprotein DNA duplication system (replisomes) for their existence. However, death of normal cells in our body occurs through the apoptotic process. During apoptotic process several crucial genes are downregulated with the upregulation of caspase pathways, leading to ultimate degradation of genomic DNA. In metastatic cancer cells (SKBR-3, MCF -7, and MDA-462), this process is inhibited to achieve immortality as well as overexpression of the enzymes for the synthesis of marker molecules. It is believed that the GSL of the lacto family such as LeX, SA-LeX, LeY, Lea, and Leb are markers on the human colon and breast cancer cells. Recently, we have characterized that a few apoptotic chemicals (cis-platin, L-PPMP, D-PDMP, GD3 ganglioside, GD1b ganglioside, betulinic acid, tamoxifen, and melphalan) in low doses kill metastatic breast cancer cells. The apoptosis-inducing agent (e.g., cis-platin) showed inhibition of DNA polymerase/helicase (part of the replisomes) and also modulated (positively) a few glycolipid-glycosyltransferase (GSL-GLTs) transcriptions in the early stages (within 2 h after treatment) of apoptosis. These Lc-family GSLs are also present on the surfaces of human breast and colon carcinoma cells. It is advantageous to deliver these apoptotic chemicals through the metastatic cell surfaces containing high concentration of marker glycolipids (Lc-GSLs). Targeted application of apoptotic chemicals (in micro scale) to kill the cancer cells would be an ideal way to inhibit the metastatic growth of both breast and colon cancer cells. It was observed in three different breast cancer lines (SKBR-3, MDA-468, and MCF-7) that in 2 h very little apoptotic process had started, but predominant biochemical changes (including inactivation of replisomes) started between 6 and 24 h of the drug treatments. The contents of replisomes (replisomal complexes) during induction of apoptosis are not known. It is known that DNA helicase activities (major proteins catalyze the melting of dsDNA strands) change during apoptotic induction process. Previously DNA Helicase-III was characterized as a component of the replication complexes isolated from carcinoma cells and normal rapid growing embryonic chicken brain cells. Helicase activities were assayed by a novel method (combined immunoprecipitation-ROME assay), and DNA polymerase-alpha activities were determined by regular chain extension of nicked "ACT-DNA," by determining values obtained from +/- aphidicolin added to the incubation mixtures. Very little is known about the stability of the "replication complexes" (or replisomes) during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during replication, repair, and recombination processes. In all three breast carcinoma cell lines (SKBR-3, MCF-7, and MDA-468), a common trend, decrease of activities of DNA polymerase-alpha and Helicase-III (estimated and detected with a polyclonal antibody), was observed, after cis-platin- and L-PPMP-induced apoptosis. Previously our laboratory has documented downregulation (within 24-48 h) of several GSL-GLTs with these apoptotic reagents in breast and colon cancer cells also. Perhaps induced apoptosis would improve the prognosis in metastatic breast and colon cancer patients.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/patología , ADN Helicasas/genética , ADN Polimerasa I/genética , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Embrión de Pollo , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos

RESUMEN

Metal-based drugs remain a tiny minority of all drugs that are on the market. The success story of the quintessential metal-based drug cisplatin (CP), which is intravenously administered to 70% of all cancer patients, however, demonstrates the inherent potential of metal-based drugs. A distinct disadvantage of CP is the dose-limiting severe toxic-side effects that it exerts in patients. To better understand the biomolecular basis for its toxicity, we employed a metallomics method to observe all platinum metabolites that are formed in blood plasma. These investigations revealed that a highly toxic CP-derived hydrolysis product - the highly toxic monoaqua hydrolysis complex (MHC) - is formed within 5min. More importantly, the application of this research tool has unraveled the mechanisms by which the chemoprotective agents sodium thiosulfate, d-methionine, N-acetyl-cysteine and l-glutathione modulate the metabolism of CP in plasma, namely by rapidly reacting with the MHC to form platinum­sulfur complexes. Since CP remained in plasma for a considerable time, the possibility of 'tuning' its metabolism with chemoprotective agents in a desirable way has emerged. These observations are highly relevant because these chemoprotective agents were previously shown to significantly reduce the toxicity of CP in animal models, often without appreciably affecting its anticancer efficiency. Collectively, these results suggest that the toxicity of other metal-based drugs may be overcome if their metabolism in the bloodstream is adequately tuned with a suitable chemoprotective agent. This principle strategy has considerable potential in terms of harnessing the full potential of bringing more metal-based drugs to the market.

Asunto(s)

Antineoplásicos/farmacología , Cisplatino/farmacología , Sustancias Protectoras/farmacología , Compuestos de Azufre/farmacología , Acetilcisteína/química , Acetilcisteína/farmacología , Animales , Antineoplásicos/sangre , Antineoplásicos/toxicidad , Cisplatino/sangre , Cisplatino/toxicidad , Glutatión/química , Glutatión/farmacología , Humanos , Metionina/química , Metionina/farmacología , Sustancias Protectoras/química , Compuestos de Azufre/química , Tiosulfatos/química , Tiosulfatos/farmacología

RESUMEN

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

Asunto(s)

Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas del Metal/administración & dosificación , Platino (Metal)/administración & dosificación , Animales , Antioxidantes/metabolismo , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Dietilnitrosamina/toxicidad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/patología , Masculino , Metaloproteinasa 9 de la Matriz/biosíntesis , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Ratas , Proteína p53 Supresora de Tumor/biosíntesis

RESUMEN

Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the world best selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. In this article we have highlighted the anticancer activity of the organotin(IV) carboxylates published in the last few years (from 2008 to 2016). In most cases they present lower IC50 values than those of cisplatin, which indicates their high activity against the cancer cell lines. The summarized data reveal that every year new organotin(IV) carboxylate complexes are synthesized with the aim of new anticancer agent with much better results than the than the corresponding activity of cis-platin or other clinically approved drugs. In addition to the advantages of high activity, compared to the platinum compound, tin complexes are much cheaper. Thus by using organotin carboxylate for clinical medicine, cost reduction, dosage reduction and effect enhancement will be reached.

Asunto(s)

Antineoplásicos/uso terapéutico , Ácidos Carboxílicos/química , Neoplasias/tratamiento farmacológico , Compuestos Orgánicos de Estaño/uso terapéutico , Antineoplásicos/química , Humanos , Compuestos Orgánicos de Estaño/química

RESUMEN

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds having anticancer action. Among the many metal compounds synthesized and tested, those based on titanium have received considerable attention because of their cytotoxic activity against solid tumors. Particularly, new titanocene compounds containing aromatic groups linked to the Cp (cyclopentadienyl ring, C5H5) have been synthetized, such as the titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium dichloride) that displayed promising medium-high cytotoxic activity on breast cancer cell lines. Other titanocene complexes recently synthesized, obtained by replacing the substituent methoxy-aryl of cyclopentadienes of titanocene Y with ethenyl-methoxide or ethenyl-phenoxide, showed increased cytotoxic activity on breast cancer cell lines being more stable compounds. In this paper, we report that new titanocene complexes holding lipophilic groups, for instance a methyl group on benzyl carbon, exhibit improved antiproliferative effect on breast cancer cell line MCF-7. Similar results have been obtained introducing a 5-methoxy naphthyl group to further stabilize the titanocene complexes. These inhibitory effects on breast cancer cells have been ascribed to human topoisomerase I and II inhibition as demonstrated by specific enzymatic assays.

Asunto(s)

ADN-Topoisomerasas de Tipo I/química , Proteínas de Unión al ADN/antagonistas & inhibidores , Compuestos Organometálicos/química , Inhibidores de Topoisomerasa I/química , Inhibidores de Topoisomerasa II/química , Antígenos de Neoplasias/metabolismo , Supervivencia Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo I/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/metabolismo , Humanos , Células MCF-7 , Microscopía Fluorescente , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/farmacología

RESUMEN

In recent years, widespread antisense transcripts have been identified systematically in mammalian cells and are known to regulate gene expression, although their functional significance remains largely unknown. Previous work has identified that acetylcholinesterase (AChE) is expressed aberrantly in various malignant tumors and function as a tumor growth suppressor. However, the mechanism of AChE gene regulation in tumors remains unclear. In this study, we show that the AChE antisense RNA (AChE-AS) play an important role in AChE expression regulation. An inverse relationship was identified between AChE-AS and AChE expression in hepatocellular carcinoma and hepatoma cells. The silenced AChE-AS corresponds to elevated expression of AChE. Furthermore, we demonstrated that reduced AChE-AS increased H3K4 methylation and decreased H3K9 methylation in the AChE promoter region. As expected, elevated AChE levels induced by inhibition of AChE-AS enhanced anticarcinogen-induced apoptosis. These observations demonstrated that AChE-AS modulates AChE expression and exerts an anti-apoptotic effect through direct repression of AChE expression in HCC cells. Thus, natural antisense RNA may play an important role in AChE regulation via affecting the epigenetic modification in the AChE promoter region.

Asunto(s)

Acetilcolinesterasa/genética , Carcinoma Hepatocelular/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , ARN sin Sentido/genética , Acetilcolinesterasa/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular , Línea Celular Tumoral , Cisplatino/farmacología , Metilación de ADN , Células Hep G2 , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Lisina/metabolismo , Metilación , Mitomicina/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Regiones Promotoras Genéticas/genética , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

Surface confined interaction of anti-cancer drug bleomycin (BLM) with nucleic acids: single stranded and double stranded DNA was investigated herein by using electrochemical impedance spectroscopy (EIS) technique in combination with a graphite sensor technology. The experimental conditions were optimized: such as, dsDNA concentration, BLM concentration and interaction time. The main features of impedimetric DNA biosensor, such as its detection limit and the repeatability, were also discussed. The in situ interaction of BLM with dsDNA was also tested impedimetrically in the absence or presence of other chemotherapeutic agents, such as mitomycin C (MC) and cis-platin (cis-DDP) for testing the selectivity.

Asunto(s)

Antineoplásicos/química , Bleomicina/química , ADN/química , Antineoplásicos/metabolismo , Técnicas Biosensibles , Bleomicina/metabolismo , ADN/metabolismo , Espectroscopía Dieléctrica , Impedancia Eléctrica , Electroquímica

RESUMEN

The Schiff base, 3-hydroxy-4-{[4-(methylsulfanyl)phenyl]imino}-3,4-dihydronaphthalen-1(2H)-one, and its Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes have been synthesized and characterized by microanalysis, conductance, (1)H NMR, infrared and electronic spectral measurements. The ligand exists in the ketoimine form in chloroform, and in the enolimine form in the solid state, as shown by (1)H NMR and IR spectroscopies. The ligand coordinates to the metal ions in the ratio 1:1, using NO chromophores forming complexes of the type [MLNO3]H2O, with the exception of the Zn(II) and Pd(II) complexes. Electronic measurements are indicative of a four coordinate square-planar geometry for all the complexes, except for the Cu(II) and Zn(II) complexes which assume a tetrahedral geometry. None is an electrolyte in nitromethane. The ligand and the metal complexes are air-stable, but decomposed on heating at 120 °C and in the range 150-156 °C respectively. The antibacterial studies reveal that the Co(II) and the Cu(II) complexes exhibit broad-spectrum activity against Proteus mirabilis, Escherichia coli and Staphylococcus aureus with inhibitory zones range of 14.0-22.0 and 13.0-25.0 mm respectively. The antiproliferative studies show that the Zn(II) complex has the best in-vitro anticancer activity against both HT-29 (colon) carcinoma and MCF-7 (human breast) adenocarcinoma with IC50 values of 6.46 µm and 3.19 µm, which exceeds the activity of Cis-platin by 8 % and 63 % respectively.

RESUMEN

Aim To establish a modified method of tissue digestion and cis-platin concentration measurement in tissue by atomic absorption spectrometry.Methods Using shimadzu atomic absorption spectrometry system and under the conditions of AA-6300 atomic absorption spectrophotometer,GFA-Ex7i graphite furnace,ASC-6100 automatic sampler and platinum hollow cathode discharge lamp,the cisplatin concentration of the tissues containing loading cisplatin magnetic nanomedicine which were digested with nitric acid and hydrogen peroxide in water bath,was measured by atomic absorption spectrophotometer at 265.9 nm.Results The concentrations of cis-platin in different tissues were in the linear range of 54~283.5 ?g?L-1;all the correlation coefficient were larger than 0.999 and all the inter-day and intro-day variation coefficient were smaller than 5%.Conclusion The modified method of tissue digestion and atomic absorption spectrometry applied is of high precision and efficiency, suitable for the pharmacokinetic research on cis-platin.

RESUMEN

The present study has been undertaken to pursue the cytotoxic effects of cis-Platin on the osteoid formation in metaphysis of rat tibia. By using the immunohistological staining method for type I collagen in rat tibial osteoid, the author detected the deposition of type I collagen, which is the collagenous constituent of endochondral osteoid, after administration of cis-Platin in experimental animals. For the immunological reactions of type I collagen, we used the rabbit anti-rat collagen type I polyclonal antibody as primary antibody and biotinylated goat anti-rabbit IgG as secondary antibody. The distributions of immunohistological reactions in the each of metaphyseal osteoids were analyzed with an image analyzer, and we studied the variances of type I collagens by statistical probabilities. In 12 hours after cis-Platin injection, immunoreactive area in the osteoid of metaphysis was distinctly decreased. Immunoreactive area of type I collagen in osteoids of 1 day and 3 days group metaphysis was increased more than that of 12 hours group and the type I collagen in the metaphysis showed weak immunoreactions of type I collagens with an image analyzer. In the osteoids of 7 days group after cis-Platin injection, the immunoreactive area was similar to that of control group. It is consequently suggested that cis-Platin would induce the decrease of type I collagen in the osteoid. But the type I collagen in tibial osteoid shows the increase from a few days after cis-Platin injection.

Asunto(s)

Animales , Ratas , Colágeno , Colágeno Tipo I , Cabras , Inmunoglobulina G , Tibia