Abstract
Resistance acquired toward anti-cancer agents is a significant drawback in breast cancer therapy. A key factor contributing to drug resistance is apoptosis suppression associated with the upregulation of anti-apoptotic Bcl-2 family proteins. Specifically, the anti-apoptotic Mcl-1 protein has been shown to play a significant role in drug resistance, making it an important therapeutic target. The present study aimed at determining the antiproliferative activity of 3-chloroplumbagin (ChPL), a naphthoquinone derived from a Dionaea sp., toward breast cancer cells and examining the involvement of Mcl-1 inhibition in ChPL-induced cell death. The results showed that ChPL inhibited breast cancer cell proliferation and induced apoptosis through the intrinsic pathway through down-regulation of anti-apoptotic Bcl-2 family proteins. The induction of apoptosis by ChPL was found to be mediated through MAP kinase signaling inhibition. ChPL inhibited the phosphorylation of MEK and ERK proteins in breast cancer cells, and increased apoptosis induction in cells with reduced ERK expression. Furthermore, ERK silencing decreased the expression of Mcl-1 in ChPL-treated cells. The results of this research indicate that ChPL induces apoptosis in breast cancer cells through MAPK-mediated Mcl-1 inhibition, suggesting further research into its potential in breast cancer treatment.
Highlights
Breast cancer is among the most frequently diagnosed cancers in the female population
Mcl-1 is an anti-apoptotic protein of the Bcl-2 protein family, which participates in regulating the intrinsic apoptotic pathway (IAP) (Han et al, 2004)
The intrinsic pathway is characterized by mitochondria outer membrane permeabilization (MOMP) which
Summary
Breast cancer is among the most frequently diagnosed cancers in the female population. The upregulation of the anti-apoptotic Bcl-2 family proteins has been shown to suppress cell death induced by cytotoxic anticancer drugs (Yip and Reed, 2008). This renders the anti-apoptotic Bcl-2 proteins important targets in cancer drug design (Yip and Reed, 2008). Recent research has pointed to the importance of targeting the anti-apoptotic Bcl-2 family protein, Mcl-1 (Willis et al, 2005). The MAP kinase signaling pathway, which plays an important role in breast cancer progression, has been shown to regulate Mcl-1 expression (Mueller et al, 2000). MAP kinase activation increases Mcl-1 expression leading to cell survival, implicating the role of Mcl-1 in apoptotic cancer cell evasion and breast cancer therapeutic resistance (Williams and Cook, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
