A review on endoplasmic reticulum-dependent anti-breast cancer activity of herbal drugs: Possible challenges and opportunities.

Abstract

Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Its management includes the use of chemotherapeutic agents, radiation, and surgery. The use of chemotherapeutic agents in BC is costly, and they possess several adverse effects. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The generation of endoplasmic reticulum (ER) stress disturbs homeostasis in the ER lumen due to the accumulation of misfolded proteins, leading to the activation of unfolded protein response (UPR), which aims to restore ER homeostasis. However, in the case of searing ER stress, UPR activates three stress-detecting proteins: IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. Subsequently, there are two ways to achieve antitumor effects by ER stress modulation: first, by suppressing the adaptive UPR to make cells susceptible to ER stress, and second, by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Previous studies have explored several Herbal drugs and their active constituents to deliver effective, non-toxic, and cost-effective anti-cancer therapy. Increased evidence suggests that several herbal drugs have been shown to trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of twenty-four Herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells, thereby inducing apoptosis through the modulation of the ER stress-related protein response. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC.