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Front. Pharmacol. | doi: 10.3389/fphar.2019.00784

3-Chloroplumbagin induces cell death in breast cancer cells through MAPK-mediated Mcl-1 inhibition

 Anna Kawiak1*, Anna Domachowska1, Aleksandra Krolicka1,  Monika Smolarska1 and  Ewa Lojkowska1
  • 1University of Gdansk, Poland

Resistance acquired towards anti-cancer agents is a major 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. The phosphorylation of MEK and ERK proteins was inhibited by ChPL in breast cancer cells and ChPL-induced apoptosis increased 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.

Keywords: Apoptosis, breast cancer, MAPK pathway, Mcl-1, plumbagin derivatives

Received: 13 Feb 2019; Accepted: 17 Jun 2019.

Edited by:

Amit K. Tiwari, University of Toledo, United States

Reviewed by:

Sonia Emanuele, University of Palermo, Italy
Md Kamal Hossain, University of Toledo, United States  

Copyright: © 2019 Kawiak, Domachowska, Krolicka, Smolarska and Lojkowska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Anna Kawiak, University of Gdansk, Gdansk, 80-952, Pomeranian Voivodeship, Poland, anna.kawiak@biotech.ug.edu.pl