Pharmacological Research ( IF 9.1 ) Pub Date : 2019-06-26 , DOI: 10.1016/j.phrs.2019.104330 Momita Das , Raghuram Kandimalla , Bhaskarjyoti Gogoi , Krishna Nayani Dutta , Paramita Choudhury , Rajlakshmi Devi , Partha Pratim Dutta , Narayan Chandra Talukdar , Suman Kumar Samanta
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.
中文翻译:
膳食植物化学物质马哈宁(Mahanine)可通过抑制乳腺癌干细胞的自我更新来抑制大鼠的乳腺肿瘤负担并抑制亚型,无论乳腺癌的进展如何
从可食用植物(Murraya koenigii)中分离出的咔唑生物碱Mahanine(MH)可能在体外抑制乳腺癌细胞亚型改变的生长,并显着降低了N-甲基-N-亚硝基脲(MNU)诱导的乳腺肿瘤负担鼠。实验结果表明,用于治疗的24小时20 - 25μMMH的是非常有效的,以减少通过细胞凋亡的细胞的增殖与阻止所述细胞在G中0 / G 1在两个ER + / p53的WT MCF-7和三阴性/ p53 MutMDA-MB-231细胞。另一方面,暴露于这两种细胞系的10–15μMMH导致了乳腺球形成的抑制和CD44高/ CD24低/上皮特异性抗原阳性(ESA +)群体的减少,最终导致自我丧失干细胞的更新能力。此外,体内观察表明,以50mg / kg体重的剂量腹膜内注射MH四周,一周内三次,显着(P = 0.03)降低了MNU诱导的大鼠的乳腺肿瘤重量。总而言之,这项研究提供了新的见解,探讨了MH介导的生长停滞机制与亚型无关的乳腺癌进展。