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High-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer, accounting for 70%–80% of mortality. However, the treatment of HGSOC has improved little in the past few decades. Metformin is the first-line medication for the treatment of type 2 diabetes and has now gained more attention in cancer treatment. In this study, we sought to identify potential hub genes that metformin could target in the treatment of HGSOC. We downloaded GSE69428 and GSE69429 in the Gene Expression Omnibus database and performed the bioinformatics analysis. Subsequently, we analyzed the effect of Metformin in HGSOC through biological experiments. Molecular simulation docking was used to predict the interaction of Metformin and CCNE1. We chose CCNE1 for the study based on bioinformatics analysis, literature studies, and preliminary data. We evaluated that CCNE1 is overexpressed in HGSOC tissues and found that HGSOC cells with high CCNE1 expression increase sensitivity to Metformin treatment in the analysis of cell proliferation and anchorage-independent growth. Metformin could inhibit the expression of CCNE1, which is associated with the anti-proliferative effect of tumor cells. Moreover, Metformin could ameliorate the tumor growth in syngeneic orthotopic transplantation mouse models and xenograft tumorigenesis models. Furthermore, molecular simulation docking showed that Metformin may bind to CCNE1 protein, suggesting that CCNE1 could be a potential target for Metformin. Our data revealed that Metformin has antitumor effects on ovarian cancer and CCNE1 could be a potential target for Metformin. [ABSTRACT FROM AUTHOR]

Uncontrolled cell proliferation is a common feature of human cancer. Some of herbal extract or plant-derived medicine had been shown as an important source of effective anticancer agents. We previously reported that an n-BuOH-soluble fraction of Kalanchoe tubiflora has antiproliferative activity by inducing mitotic catastrophe. In this study, we showed that the H2O-soluble fraction of Kalanchoe tubiflora (KT-W) caused cell cycle arrest, and senescence-inducing activities in A549 cells. We used 2 dimensional PAGE to analyze the protein expression levels after KT-W treatment, and identified that the energy metabolism-related proteins and senescence-related proteins were disturbed. In vivo experiments showed that the tumor growths in A549-xenografted nude mice were effectively inhibited by KT-W. Our findings implied that KT-W is a putative antitumor agent by inducing cell cycle arrest and senescence. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1663-1673, 2016. [ABSTRACT FROM AUTHOR]

Amounting evidence has demonstrated that phenethyl isothiocyanate (PEITC) is a strong inducer of reactive oxygen species (ROS) and functions as a selective killer to various human cancer cells. However, it remains obscure whether PEITC has potential selective lethality to malignant glioma cells. Thus in this study, we performed multiple analysis such as MTT assay, Hoechst 33258 staining, flow cytometry, foci formation, RT-PCR, Western blot, and transfection to explore the selective lethality of PEITC to malignant glioma cells and the underlying mechanisms. We found that PEITC induced a selective apoptosis and suppressed tumorigenicity and migration of malignant glioma cells. Furthermore, we found PEITC significantly induced GSH depletion, ROS production, caspase-9 and caspase-3 activation, and miR-135a upregulation in malignant glioma cells but not in normal cells. Moreover, PEITC activated the miR-135a-mitochondria dependent apoptosis pathway as demonstrated by downregulation of STAT6, SMAD5 and Bcl-xl while upregulation of Bax expression and Cytochrome-C release in malignant glioma cell lines but not in the immortalized human normal glial HEB cells. Correspondingly, the above PEITC-induced activation of the ROS-MiR-135a-Mitochondria dependent apoptosis pathways in malignant glioma was attenuated by pre-transfection with miR-135a inhibitor, pre-treatment with multidrug resistance-associated protein 1 (MRP1) inhibitor Sch B, or combination with glutathione (GSH). These results revealed that PEITC selectively induced apoptosis of malignant glioma cells through MRP1-mediated export of GSH to activate ROS-MiR-135a-Mitochondria dependent apoptosis pathway, suggesting a potential application of PEITC for treating glioma.