Mahanine, A dietary phytochemical, represses mammary tumor burden in rat and inhibits subtype regardless breast cancer progression through suppressing self-renewal of breast cancer stem cells

Abstract

Mahanine (MH), a carbazole alkaloid isolated from an edible plant (Murraya koenigii), potentially inhibits the growth of altered subtypes of breast cancer cells in vitro and significantly reduced the mammary tumor burden in N-Methyl-N-nitrosourea (MNU) induced rat. The experimental results showed that 20–25 μM of MH for 24 h of treatment was very potent to reduce the cell proliferation through apoptosis with arresting the cells in G0/G1 in both ER+/p53WT MCF-7 and triple negative/p53Mut MDA-MB-231 cells. On the other hand, 10–15 μM of MH exposure to those two cell lines, caused inhibition of mammosphere formation and reduction of CD44high/CD24low/epithelial-specific antigen-positive (ESA+) population, which ultimately led to loss of self-renewal ability of breast cancer stem cells. Further, in vivo observation indicated that intraperitoneal injection of MH for four weeks with a dose of 50 mg/kg body weight thrice in a week, significantly (P = 0.03) reduced the mammary tumor weight in MNU induced rat. In conclusion, this study provides the novel insight into the mechanism of MH mediated growth arrest in subtype irrespective breast cancer progression.