Sajadian Saharolsadat, Vatankhah Melody, Majdzadeh Maryam, Kouhsari Shide Montaser, Ghahremani Mohammad Hossein, Ostad Seyed Nasser
a Department of Biology, Faculty of Science , University of Tehran , Tehran , Iran and.
b Department of Toxicology & Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
Toxicol Mech Methods. 2015;25(5):388-95. doi: 10.3109/15376516.2015.1045656. Epub 2015 May 18.
Previous report of the vast effectiveness of opium derivatives in cancer therapy is leading us to see possible effects of these derivatives on cancer stem cells in order to find new agent for cancer therapy. In this study, cells were stained for CSC markers and sorted by magnetic beads. CSCs exhibit the characteristic CD44(+)/CD24(-/low)/ESA(+) phenotype. Noscapine and papaverine (alkaloids) showed anti-proliferative activity on MCF-7 and MDA-MB-231 cell lines. It was observed that noscapine has more cytotoxic effect on CSC derived from both cell lines compared with their parental cells. Papaverine has more cytotoxic effect on MCF-7 CSCs in comparison with parental cells, while CSCs population of MDA-MB-231 is more resistant to papaverine compared with MDA-MB-231 cells. Noscapine enhances apoptosis in MDA-MB-231 CSCs more than parent cells, while in MCF-7 CSCs the apoptosis is less than parent cells. Our results show that papverine is less active in terms of apoptotic effect on CSCs in both cell lines. Moreover, noscapine arrests MCF-7 and MDA-MB-231 CSCs cell cycle at G2/M phase, while papverine arrests cell cycle at G0/G1 phase. It was suggested different mechanism for apoptotic cytotoxicity. The results of this study show possible specific effects of noscapine on these breast cell lines CSCs.
先前关于鸦片衍生物在癌症治疗中具有显著疗效的报道，促使我们去探究这些衍生物对癌症干细胞的可能作用，以便寻找新的癌症治疗药物。在本研究中，细胞被标记上癌症干细胞标志物，并通过磁珠进行分选。癌症干细胞表现出CD44(+)/CD24(-/低)/ESA(+)的特征性表型。那可丁和罂粟碱（生物碱）对MCF - 7和MDA - MB - 231细胞系显示出抗增殖活性。研究发现，与亲代细胞相比，那可丁对源自这两种细胞系的癌症干细胞具有更强的细胞毒性作用。与亲代细胞相比，罂粟碱对MCF - 7癌症干细胞具有更强的细胞毒性作用，而MDA - MB - 231的癌症干细胞群体对罂粟碱的耐药性比MDA - MB - 231细胞更强。那可丁比亲代细胞更能增强MDA - MB - 231癌症干细胞的凋亡，而在MCF - 7癌症干细胞中，凋亡程度低于亲代细胞。我们的结果表明，罂粟碱对这两种细胞系的癌症干细胞的凋亡作用较弱。此外，那可丁使MCF - 7和MDA - MB - 231癌症干细胞的细胞周期停滞在G2/M期，而罂粟碱使细胞周期停滞在G0/G1期。研究提出了不同的凋亡细胞毒性机制。本研究结果显示了那可丁对这些乳腺癌细胞系癌症干细胞可能具有的特异性作用。
