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  • Fig E ects of the NAX and NAX

    2020-03-24

    Fig. 13. Effects of the NAX053 and NAX054 Compounds on the Proliferation and IC50s of MIA-PaCa-2 + pLXSN (Adh.) and MIA-PaCa-2 + WT-TP53 (Adh.) Cells in the Absence and Presence of 250 nM Metformin. Panel A) MTT analysis of MIA-PaCa-2 + pLXSN (Adh.) cells plated with different concentrations of NAX053 (solid red squares) or different concentrations of NAX053 and 250 nM metformin (solid blue triangles). Panel B) MTT analysis of MIA-PaCa-2 + WT-TP53 (Adh.) cells plated with different concentrations of NAX054 (solid red squares) or different concentrations of NAX053 and 250 nM metformin (solid blue triangles). Panel C) MTT analysis of MIA-PaCa-2 + pLXSN (Adh.) cells plated with different concentrations of NAX053 (solid red squares) or different concentrations of NAX054 and 250 nM metformin (solid blue triangles). Panel D) MTT analysis of MIA-PaCa-2 + WT-TP53 (Adh.) cells plated with different concentrations of NAX054 (solid red squares) or different concentrations of NAX054 and 250 nM metformin (solid blue triangles). All the experiments indicated in this figure were performed on the same day. These experiments were repeated 3 times and similar results were obtained.
    4. Discussion
    Metformin is a commonly prescribed drug for the treatment of type-II diabetes. It is a glucose lowering drug which is given to diabetic patients in the absence of insulin treatment. Metformin effects the AMPK pathway which regulates TSC1/TSC2/RHEB/ mTORC1 signaling and metabolism, energy, redox and Gilteritinib (Candido et al., 2018). When AMPK is activated the pro-proliferative RAS/MEK/ERK and PI3K/PTEN/AKT/mTORC1 pathways are suppressed.
    miRs have important effects on mitochondria (Li et al., 2012). One of the key targets of metformin is the mitochondria where it can alter bioenergetics (Andrzejewski et al., 2014). Metformin can have divergent effects on miR expression. Some studies have indicated that metformin may induce the expression of certain mIRs. Other investigations have indicated that metformin may suppress the expression of the same miR under different experimental conditions and divergent tissue types.
    Metformin can have profound effects on mitochondrial dysfunction in breast cancer cells (Sharma & Kumar., 2018). In these studies, metformin influenced the migration and induction of apoptosis in breast cancer cell lines. Metformin also altered the ex-pression of many genes including: BCL2, BAX, MMP2, MMP9, miR-21 and miR-155.
    Metformin can also have effects on drug-resistant prostate cancer cells by targeting mitochondrial complex-1. This was de-monstrated to impair the proliferation and invasiveness of the drug-resistant PC3-DR cells but not drug-sensitive PC3 cells. Decreased expression of miR-205 is associated with drug resistance and EMT in PC3-DR cells. Induced re-expression of miR-205 was demon-strated to shift mitochondrial oxidative phosphorylation to Warburg metabolism and resulted in increased sensitivity to docetaxel (Ippolito et al., 2016).
    Metformin can induce mitochondrial-regulated apoptosis in oral cancer cells. Metformin treatment of the oral cancer cell line KB1
    S.M. Akula, et al. Advances in Biological Regulation xxx (xxxx) xxxx
    Fig. 14. Effects of the NAX060 and NAX075 Compounds on the Proliferation and IC50s of MIA-PaCa-2 + pLXSN (Adh.) and MIA-PaCa-2 + WT-TP53 (Adh.) Cells in the Absence and Presence of 250 nM Metformin. Panel A) MTT analysis of MIA-PaCa-2 + pLXSN (Adh.) cells plated with different concentrations of NAX060 (solid red squares) or different concentrations of NAX060 and 250 nM metformin (solid blue triangles). Panel B) MTT analysis of MIA-PaCa-2 + WT-TP53 (Adh.) cells plated with different concentrations of NAX060 (solid red squares) or different concentrations of NAX060 and 250 nM metformin (solid blue triangles). Panel C) MTT analysis of MIA-PaCa-2 + pLXSN (Adh.) cells plated with different concentrations of NAX075 (solid red squares) or different concentrations of NAX075 and 250 nM metformin (solid blue triangles). Panel D) MTT analysis of MIA-PaCa-2 + WT-TP53 (Adh.) cells plated with different concentrations of NAX075 (solid red squares) or different concentrations of NAX075 and 250 nM metformin (solid blue triangles). All the experiments indicated in this figure were performed on the same day. These experiments were repeated 3 times and similar results were obtained.