3-Chloroplumbagin Induces Cell Death in Breast Cancer Cells Through MAPK-Mediated Mcl-1 Inhibition

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.

Identification of Dipeptidyl Peptidase (DPP) Family Genes in Clinical Breast Cancer Patients via an Integrated Bioinformatics Approach

“…Using BCL2 inhibitors for these metastatic cases improved cancer cell apoptosis in a preclinical model of breast cancer [ 7 , 8 ]. Genes that are involved in this biological process are dipeptidyl peptidase ( DPP ) family genes, extracellular-signal-regulated kinase ( ERK ), GATA-binding protein 3 ( GATA3 ), signal transducer and activator of transcription 3 ( STAT3 ), phosphatidylinositol 3-kinase ( PI3K ), and NOTCH [ 9 , 10 , 11 , 12 ].…”

Transformed tissue of Dionaea muscipula J. Ellis as a source of biologically active phenolic compounds with bactericidal properties

“…The healing properties of these plants arise from the ability to produce large amounts of phenolic compounds with strong biological activity (Gaascht et al 2013 ). Extracts from carnivorous plant tissues were proven to have antibacterial (Krolicka et al 2008 ; Makowski et al 2020 ), antioxidative (Królicka et al 2009 ; Makowski et al 2020 ), antifungal (Padhye et al 2010 ), and anticancer properties (Kawiak et al 2019 ). Moreover, previous phytochemical studies showed that the species most abundant in phenolic derivatives in the family Droseraceae is D. muscipula (Gaascht et al 2013 ).…”

Elicitation-Based Method for Increasing the Production of Antioxidant and Bactericidal Phenolic Compounds in Dionaea muscipula J. Ellis Tissue

“…As shown, the extracts from carnivorous plants from the family, Droseraceae, have strong antioxidant [5], antibacterial [1,6] and antifungal [7] properties. Recently, Kawiak et al [8] showed that they also have anticancer properties. Due to the growing resistance for antibiotics of some human-pathogenic microbes, and the increasing demand for new drugs in cancer therapy, plant material with strong biological activity are in great demand.…”