Botany - Research Publications

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    Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: pivotal role of superoxide dismutase (SOD)
    (Springer, 2018) Sharma, Prateek; Kumar, Sanjeev
    Purpose Despite a growing body of evidence indicating a potential efficacy of the anti-diabetic metformin as anti-cancer agent, the exact mechanism underlying this efficacy has remained largely unknown. Here, we aimed at assessing putative mechanisms associated with the ability of metformin to reduce the proliferation and migration of breast cancer cells. Methods A battery of in vitro assays including MTT, colony formation, NBT and scratch wound healing assays were performed to assess the viability, proliferation, anti-oxidative potential and migration of breast cancer-derived MCF-7, MDA-MB-231 and T47D cells, respectively. Reactive oxygen species (ROS) assays along with fluorescence microscopy were used to assess apoptotic parameters. Quantification of SOD, Bcl-2, Bax, MMPs, miR-21 and miR-155 expression was performed using qRT-PCR. Results We found that metformin inhibited the growth, proliferation and clonogenic potential of the breast cancer-derived cells tested. ROS levels were found to be significantly reduced by metformin and, concomitantly, superoxide dismutase (SOD) isoforms were found to be upregulated. Mitochondrial dysfunction was observed in metformin treated cells, indicating apoptosis. In metastatic MDA-MB-231 cells, migration was found to be suppressed by metformin through deregulation of the matrix metalloproteinases MMP-2 and MMP-9. The oncogenic microRNAs miR-21 and miR-155 were found to be downregulated by metformin, which may be correlated with the suppression of cell proliferation and/or migration. Conclusions Our data indicate that metformin may play a pivotal role in modulating the anti-oxidant system, including the SOD machinery, in breast cancer-derived cells. Our observations were validated by in silico analyses, indicating a close interaction between SOD and metformin. We also found that metformin may inhibit breast cancer-derived cell proliferation through apoptosis induction via the mitochondrial pathway. Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels. These findings may be instrumental for the clinical management and/or (targeted) treatment of breast cancer.
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    INFLUENCE OF INSULIN AND METFORMIN ON PROSTATE CANCER
    (Nova Science Publishers, 2017) Singh, Pushpendra; Bast, Felix; Kumar, Shashank; Saini, Khem Chand
    Dietary habit and hormonal factor play a significant role in prostate cancer deregulation in addition to genetic and environmental factor. Nonandrogenic growth factor like insulin and insulin growth factor are influences the prostate cancer initiation and progression. Insulin and Insulin-like growth factor regulate various metabolic pathways, cell growth, cellular proliferation and apoptosis. Various epidemiological results point out that insulin not only increased the risk of cardiovascular, macrovascular, and microvascular complications but also at significantly increase the risk of various cancers. The use of metformin, the usually approved drug for type 2 diabetes, was continually linked with the decreased risk of the incidence of a variety of cancers. More than 60 clinical trials of metformin being tested as a treatment for various types of cancer, including breast, colon, prostate, endometrial, and pancreatic cancer. The ability of metformin to lower circulating insulin may be predominantly imperative for the treatment of cancers. Moreover, metformin inhibiting mammalian target of rapamycin promoted cell growth signaling. In this chapter, the confirmation behind a role for metformin in cancer therapy and its prospective molecular mechanisms of action are discussed.