Plumbagin increases paclitaxel-induced cell death and overcomes paclitaxel resistance in breast cancer cells through ERK-mediated apoptosis induction

Anna Kawiak , Anna Domachowska , Ewa Łojkowska

Abstract

ERK is a component of mitogen-activated protein kinases that controls a range of cellular processes including cell proliferation and survival. The upregulation of ERK has been associated with apoptosis inhibition in response to various stimuli including chemotherapeutic agents. Research has suggested that the upregulation of ERK signaling by the anticancer agent paclitaxel leads to acquired resistance of cells to this compound. The presented research focused on determining the role of plumbagin, a naturally derived naphthoquinone, in the sensitization of breast cancer cells to paclitaxel-induced cell death and the involvement of ERK signaling in this process. The results of the study indicated that plumbagin increases the sensitivity of breast cancer cells to paclitaxel. Moreover, a synergistic effect between plumbagin and paclitaxel was observed. Plumbagin was shown to decrease levels of phosphorylated ERK in breast cancer cells and abrogated paclitaxel-induced ERK phosphorylation. The role of ERK in plumbagin-mediated sensitization of breast cancer cells to paclitaxel was shown through the enhancement of the synergistic effect between compounds in cells with decreased ERK expression. Furthermore, plumbagin reduced p-ERK levels in paclitaxel-resistant breast cancer cells and resensitized paclitaxel-resistant cells to this compound. These results imply that plumbagin inhibits ERK activation in breast cancer cells, which plays a role in the sensitization of cells to paclitaxel-induced cell death.
Author Anna Kawiak (IFB / IB / DBiotech)
Anna Kawiak,,
- Department of Biotechnology
, Anna Domachowska (IFB / IB / DBiotech)
Anna Domachowska,,
- Department of Biotechnology
, Ewa Łojkowska (IFB / IB / DBiotech)
Ewa Łojkowska,,
- Department of Biotechnology
Journal seriesJournal of Natural Products, ISSN 0163-3864, (A 35 pkt)
Issue year2019
Vol82
No4
Pages878-885
Publication size in sheets0.5
ASJC Classification1605 Organic Chemistry; 2707 Complementary and alternative medicine; 3002 Drug Discovery; 3003 Pharmaceutical Science; 3004 Pharmacology; 1313 Molecular Medicine; 1602 Analytical Chemistry
DOIDOI:10.1021/acs.jnatprod.8b00964
URL https://doi.org/10.1021/acs.jnatprod.8b00964
Languageen angielski
Score (nominal)35
ScoreMinisterial score = 35.0, 24-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.487; WoS Impact Factor: 2017 = 3.885 (2) - 2017=3.904 (5)
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