Triple Negative Breast Cancer (TNBC), which lacks the expression of the hormonal Estrogen Receptor (ER) and Progesterone Receptor (PR), amplification of Human Epidermal Growth Factor Receptor 2 (HER2), is not responsive to the hormonal therapy.
The results revealed that AOEE inhibited cell proliferation of the three cell lines in a concentration- and time-dependent manner.
Moreover, AOEE induces abortive autophagy through upregulation of autophagy related proteins LC3-II, Beclin-1, and p62.
Also, p16-dependent senescence was induced in AOEE treated MDA-MB-231 cells confirmed by senescence-associated β-galactosidase (SA-β-gal) expression in the treated cells.
AOEE induced activation of ERK and p38 pathways, which might be involved in autophagy and senescence induction.
Breast cancer is the most frequently diagnosed cancer in women worldwide. Triple Negative Breast Cancer (TNBC), which lacks the expression of the hormonal Estrogen Receptor (ER) and Progesterone Receptor (PR), amplification of Human Epidermal Growth Factor Receptor 2 (HER2), is not responsive to the hormonal therapy. Currently, available chemotherapy and radiotherapy cause severe side effects; therefore, there is an urgent need for new therapeutic choices for TNBC. Acridocarpus orientalis is used in folk medicine to treat several health conditions. Here, evaluated the anti-cancer activity of Acriodocarpus orientalis Ethanolic Extract (AOEE) against two TNBC (MDA-MB-231 and Hs578T) and one luminal A (MCF-7) cell lines, and investigated the molecular mechanisms underlying its anticancer activity. The results revealed that AOEE inhibited cell proliferation of the three cell lines in a concentration- and time-dependent manner. The anti-proliferative effect of AOEE was found to be concomitant with the induction of cell cycle arrest at the G1/S phase. These changes were associated with upregulation of p21WAF1 and p27 Kip1, downregulation of PCNA, Cyclin D1, phospho-Rb. Moreover, AOEE induces abortive autophagy through upregulation of autophagy related proteins LC3-II, Beclin-1, and p62. Also, p16-dependent senescence was induced in AOEE treated MDA-MB-231 cells confirmed by senescence-associated β-galactosidase (SA-β-gal) expression in the treated cells. AOEE induced activation of ERK and p38 pathways, which might be involved in autophagy and senescence induction. Acridocarpus orientalis could be a potential source for novel chemotherapeutic agents against TNBC.
