Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher

Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly (D,L-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. the efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. the influence of photosensitizer (PS) concentration (1.8-7.5 mu mol/L), incubation time (1-2 h), and laser power (10-100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 +/- 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. the InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. for a light dose of 7.5 J/cm(2) and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 +/- 3 % while for free InPc was 60 +/- 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. the nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. the participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Federal Institute of Espirito SantoFed Inst Espirito Santo, BR-29192733 Aracruz, ES, BrazilUniv Fed Espirito Santo, Hlth Sci Ctr, Biotechnol Program RENORBIO, BR-29040090 Vitoria, ES, BrazilUniversidade Federal de São Paulo, Dept Exact Sci & Earth, BR-09972270 Diadema, SP, BrazilUniv Estadual Campinas, Dept Cellular Biol, BR-13083863 Campinas, SP, BrazilUniv Fed Espirito Santo, Dept Pharmaceut Sci, BR-29040090 Vitoria, ES, BrazilUniv Estadual Campinas, Inst Chem, Dept Phys Chem, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Exact Sci & Earth, BR-09972270 Diadema, SP, BrazilWeb of Scienc

Synthetic naphthoquinone derivatives as anticancer agents in ovarian cancer: cytotoxicity assay and investigation of possible biological mechanisms action

In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their in vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3–5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4, bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3–5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK