Jenie Riris Istighfari, Amalina Nur Dina, Hermawan Adam, Suzery Meiny, Putra Agung, Meiyanto Edy
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Res Pharm Sci. 2023 Nov 23;18(6):708-721. doi: 10.4103/1735-5362.389959. eCollection 2023 Dec.
Breast cancer stem cells (BCSCs) as a kind of tumor cells are able to regenerate themselves, leading to apoptosis resistance and cancer relapse. It was reported that BCSCs contain lower levels of reactive oxygen species (ROS) associated with stemness capability. has been proposed for its chemopreventive potency against several cancer cells. This study aimed to evaluate the effects of extract (CSE) on cytotoxicity, apoptosis induction, ROS generation, and stemness markers of MDA-MB-231 and its BCSCs.
was extracted under maceration with methanol. Magnetic-activated cell sorting was used to isolate BCSCs based on CD44+ and CD24- cell surface expression. The MTT test was used to assess the cytotoxic effects of CSE on MDA-MB-231 and BCSCs. Moreover, flow cytometry was used to examine the cell cycle distribution, apoptosis, ROS level, and CD44/CD24 level. Using qRT-PCR, the gene expression of the stemness markers , and was assessed.
FINDINGS/RESULTS: We found that MDA-MB-231 contains 80% of the BCSCs population, and CSE showed more potent cytotoxicity toward BCSCs than MDA-MB-231. CSE caused apoptosis in MDA-MB-231 and BCSCs cells by increasing the level of ROS. Furthermore, CSE significantly reduced the MDA-MB-231 stemness marker CD44+/CD24- and the mRNA levels of pluripotent markers of cells in BCSCs.
CSE potentially reduces BCSCs stemness, which may be mediated by the elevation of the ROS levels and reduction of the expression levels of stemness transcription.
乳腺癌干细胞（BCSCs）作为一种肿瘤细胞，能够自我更新，导致抗凋亡和癌症复发。据报道，BCSCs中活性氧（ROS）水平较低，这与干细胞能力相关。 因其对多种癌细胞的化学预防作用而被提出。本研究旨在评估 提取物（CSE）对MDA-MB-231及其BCSCs的细胞毒性、凋亡诱导、ROS生成和干性标志物的影响。
采用甲醇浸渍法提取 。基于CD44 +和CD24 -细胞表面表达，使用磁激活细胞分选法分离BCSCs。MTT试验用于评估CSE对MDA-MB-231和BCSCs的细胞毒性作用。此外，流式细胞术用于检测细胞周期分布、凋亡、ROS水平和CD44/CD24水平。使用qRT-PCR评估干性标志物 、 和 的基因表达。
我们发现MDA-MB-231中含有80%的BCSCs群体，CSE对BCSCs的细胞毒性比对MDA-MB-231更强。CSE通过提高ROS水平诱导MDA-MB-231和BCSCs细胞凋亡。此外，CSE显著降低了MDA-MB-231干性标志物CD44 + /CD24 -以及BCSCs中细胞多能性标志物的mRNA水平。
CSE可能降低BCSCs的干性，这可能是由ROS水平升高和干性转录表达水平降低介导的。
