BI2536--A PLK inhibitor augments paclitaxel efficacy in suppressing tamoxifen induced senescence and resistance in breast cancer cells

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
B N Prashanth KumarMahitosh Mandal

Abstract

Tamoxifen resistance is a multifaceted phenomenon, characterized by the constitutive activation of multiple signaling cascades that provide an additional survival advantage to cells. Ground studies related to reverse the tamoxifen resistance by employing chemotherapeutic drugs that specifically inhibit proteins, those of aberrantly expressed, are required. Seminal studies showed that p38 signaling and VEGF play crucial role in acquiring resistance to tamoxifen. In this view, we had chosen paclitaxel, a mitotic inhibitor with anti-proliferative effects against a wide array of cancers in this study. Further to mitigate the undesirable complications of paclitaxel (PAC), we employed this drug in combination along with BI2536 (BI), a PLK inhibitor for this study to sensitize the tamoxifen resistant cells to apoptosis. MCF 7/TAM and T-47D/TAM cells were treated with PAC, BI and in combination (BI-PAC) evaluated for its anticancer activity through apoptotic and western blot analysis. Modulatory effects of BI-PAC on p38 inactivation were affirmed through immunofluorescence and drug potential studies. Results reveal that cells were subjected to apoptosis on drug(s) treatment which was confirmed through cytotoxicity, annexin studies. Fur...Continue Reading

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Citations

Mar 10, 2018·Cancers·Prashanth K B NageshMurali M Yallapu
Apr 18, 2018·International Journal of Cancer. Journal International Du Cancer·Ka-Kui ChanAnnie Nga-Yin Cheung
Jun 5, 2019·International Journal of Molecular Sciences·Yu-Hsuan LeeRong-Jane Chen
Jan 24, 2020·Scientific Reports·Prashanth K B NageshMurali M Yallapu
Nov 30, 2018·Journal of Cellular Physiology·Zihao ChenHongping Ju
Jul 9, 2021·Apoptosis : an International Journal on Programmed Cell Death·Xiaofeng DaiJianying Zhang
Sep 26, 2019·ACS Applied Materials & Interfaces·Prashanth K B NageshMurali M Yallapu

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