Nitric Oxide Synthase Potentiates the Resistance of Cancer Cell Lines to Anticancer Chemotherapeutics

Background Despite the advancement in the fields of medical science and molecular biology, cancer is still the leading cause of death worldwide. Chemotherapy is a choice for treatment; however, the acquisition of chemo-resistance is a major impediment to cancer management. Many mechanisms have been postulated regarding the acquisition of chemo-resistance in breast cancer the impact on cellular signaling and the induction of apoptosis in tumour cells. The mechanism of the apoptotic mutation of p53 and bcl-2 proteins is commonly associated with increased resistance to apoptosis and, therein, to chemotherapy. Objectives The current study was aimed to investigate A172 and MDA-MB-231 cancer cells' sensitivity against chemotherapeutic drugs, including cisplatin, doxorubicin, and paclitaxel with different doses. Moreover, it estimates the resistance of cancer cells by evaluating nitric oxide synthase (NOS) expression and evaluate its correlation with the expression profile proteins of the apoptosis regulating Bcl-2 family. Methods Dose-dependent sensitivity to cisplatin, doxorubicin, or paclitaxel was evaluated on spheroid cultured A172 and MDA-MB-231 cells lines as measured by time-lapse microscopy over a 72h period. Expressions of two nitric oxides (NO) synthases isoforms (iNOS, eNOS), anti-apoptotic (Bcl-2, phospho-Bcl-2, Mcl-1, and Bcl-xL), and pro-apoptotic (BID, Bim, Bok, Bad, Puma, and Bax) were evaluated by Western blot. The effect of NO modulation on anti- and pro-apoptotic molecule expression was also studied using Western blot. Result A172 cells show more resistance to chemotherapy drugs than MDA-MB-231 cancer cells. Therefore, they need higher doses for apoptosis. Resistance of gliomas might be returned to the higher significant expression of endothelial eNOS expression. It was clear that there is not a significant effect of NO modulation on the expression of pro-and anti-apoptotic proteins on both cell lines. Conclusion The present work provides a putative mechanism for the acquisition of drug resistance in breast cancer and glioma, which might be significant for clinical outcomes.