Vanadium rutin complex sensitizes breast cancer cells via modulation of p53/Bax/Bcl2/VEGF correlated with apoptotic events

Abstract

In pursuit of a novel approach in breast cancer therapy, we explored the ability of vanadium-rutin complex to eradicate cancer by efficiently targeting various apoptotic pathways on human breast cancer cell lines. We provide direct proof of the chemotherapeutic potential of the vanadium-rutin complex by activating p-53 dependent intrinsic apoptosis and modulating the VEGF pathways. The complex was also capable of binding and cleaving CT-DNA at different concentrations. The complex was able to inhibit cell viability at 100 and 150 µM doses in both MCF7 and MDA-MB-231 cells. Furthermore, the complex successfully initiated apoptosis in both cell lines by activating the p53 dependent intrinsic apoptotic pathway. In vitro studies also established that the complex modulated p53, Bax, Bcl2 and VEGF expressions and induced DNA fragmentation in both the cell lines.

Pharmacological Properties of 2,4,6-Trihydroxy-3-Geranyl Acetophenone and the Underlying Signaling Pathways: Progress and Prospects

“…Specifically, rutin increased GSH level and activities of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), as well as decreased malondialdehyde level ( Caglayan et al, 2019 ). As it has been demonstrated that rutin was not only able to induce pro-apoptotic effect in cancer cells via similar mechanisms as tHGA ( Iriti et al, 2017 ; Hasani et al, 2018 ; Saleh et al, 2018 ; Kunjiappan et al, 2019 ; Haifeng et al, 2020 ), but also capable of inhibiting xenobiotic-induced apoptosis in normal cells ( Caglayan et al, 2019 ), therefore it is probable that tHGA may be able to suppress xenobiotic-induced apoptosis in normal cells as well. As such, it would be worthwhile to investigate the effect of tHGA on xenobiotic-induced apoptosis in normal cells for future studies.…”

“…Rutin, a bioactive plant flavonoid and natural antioxidant, has been well reported to induce apoptosis in various cancer cells including MCF-7 human breast cancer cells (Iriti et al, 2017;Hasani et al, 2018;Saleh et al, 2018;Kunjiappan et al, 2019;Haifeng et al, 2020). Similar to tHGA, rutin exhibited its pro-apoptotic effect in MCF-7 cells by increasing Bax expression, GSH level, caspase cascade activation and chemosensitivity, as well as decreasing Bcl-2 expression (Iriti et al, 2017;Hasani et al, 2018;Saleh et al, 2018;Kunjiappan et al, 2019;Haifeng et al, 2020). However, in contrast to tHGA, rutin was capable of inhibiting mercury-induced apoptosis in normal cells (Caglayan et al, 2019).…”

“…It is important to highlight that current studies of tHGA on apoptosis were limited to in vitro model of cancer cells ( Cho et al, 2012a ; Cho et al, 2012b ) and the effect of tHGA on xenobiotic-induced apoptosis in normal cells remains unknown. Rutin, a bioactive plant flavonoid and natural antioxidant, has been well reported to induce apoptosis in various cancer cells including MCF-7 human breast cancer cells ( Iriti et al, 2017 ; Hasani et al, 2018 ; Saleh et al, 2018 ; Kunjiappan et al, 2019 ; Haifeng et al, 2020 ). Similar to tHGA, rutin exhibited its pro-apoptotic effect in MCF-7 cells by increasing Bax expression, GSH level, caspase cascade activation and chemosensitivity, as well as decreasing Bcl-2 expression ( Iriti et al, 2017 ; Hasani et al, 2018 ; Saleh et al, 2018 ; Kunjiappan et al, 2019 ; Haifeng et al, 2020 ).…”