Apoptosis promoting activity of selected plant steroid in MRMT-1 breast cancer cell line by modulating mitochondrial permeation pathway

Abstract

Escape from apoptosis is one of the main demeanor characteristics of cancer cells. Mitochondria are key players in initiating and regulating the intrinsic apoptosis pathway. Hexokinase2 (HK2) is ubiquitously expressed in several cancer cells and is essential for cell survival and death. The binding of HK2 to mitochondria promotes cell proliferation, while AKT-1 mediated pathway is crucial in this process. Peimine, a steroidal alkaloid derived from plant steroids, is screened for docking properties, ADMET properties, and drug-likeness. Apoptosis targets are predicted by network pharmacology using 47 genes associated with apoptosis. According to in silico study, peimine has the potential for dual Targeting on HK2 and AKT1. For further confirmation, peimine was subjected to Cell culture studies using MRMT-1 rat breast cancer cells. The elevated levels of cytochrome c and Caspase 9 activity indicate that the intrinsic apoptosis pathway causes cell death. The decreased glucose uptake by the MRMT-1 cells indicates that pimine inhibits glucose transport by inhibiting the membrane HK2.