Proposed model of the mechanisms of action of male M

Proposed model of the mechanisms of action of male M. pomifera extracts on ER-positive MCF-7 and T47D breast cancer cells. (1) Plant extract activates TRPV1, inducing calcium influx into cells. The elevated intracellular calcium triggers several apoptotic pathways, the mitochondria-mediated intrinsic pathway, extrinsic FAS-FADD and ERK-induced pathways, and ER-stress mediated pathway. (1a) The accumulation of Ca2+ into mitochondria causes the transient depolarization of mitochondrial membrane potential. As a result, the mitochondrial permeability transition pores (MPTPs) open and release cytochrome c (cyt c), leading to caspase activation, increasing proapoptotic proteins BAK/BAX, decreasing anti-apoptotic BCL-2, and leading to apoptosis. (1b) Calcium influx triggers the extrinsic pathway by activating FAS, FADD, caspase 8, and caspase 3, and leading to apoptosis. It may be that plant extracts activate the FAS/FADD pathway directly (2). (1c) TRPV1 also activates the epidermal growth factor receptor (EGFR), further activating ERK. Phosphorylated ERK then activates caspases by inducing mitochondrial intrinsic apoptosis. (1d) Plasma membrane TRPV1 activation and calcium influx lead to endoplasmic reticulum (ER) stress. ER TRPV1 becomes another source of calcium release in the cell. ER stress activates PERK, phosphorylated PERK (pPERK) activates ATF4, and ATF4 activates CHOP, leading to PERK-ATF4-CHOP-mediated apoptosis

Publication

TRPV1-Dependent Antiproliferative Activity of Dioecious Maclura pomifera Extracts in Estrogen Receptor-Positive Breast Cancer Cell Lines Involves Multiple Apoptotic Pathways (2024) Mafia Mahabub Rumpa, et al. Int J Mol Sci. 2024 May;25(10). Figure: F11. Homo sapiens

Disease mentions