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.

Our findings may contribute to design of new therapeutic strategies for the management of HCC.

Specific GABAergic interneurons in the hilus are lost in animal models with temporal-lobe epilepsy (TLE). Some preclinical evidence has indicated that GABAergic cells may provide relief from seizures in these models. This study was aimed to examine the ability of ethosuximide, an anticonvulsant drug, to promote neurogenesis in 3-day-old rat forebrain cortex stem cells. Most of the cells were found to be nestin-positive undifferentiated neural stem cells prior to their exposure to ethosuximide. It was noted that the number and percentage of tubulin β-III immunopositive neurons were increased after 6 days treatment with ethosuximide. Upon bFGF withdrawal, exposure to ethosuximide differentiated the stem cells to MAP2 positive neural cells (7.18 ± 0.43, 21.766 ± 0.55 and 41.57 ± 0.5 for control, 0.1 and 1 μM, respectively). GABA immunofluorescence images illustrated that ethosuximide increased GABAergic neurons (7.19 ± 0.32, 23.23 ± 0.55, and 46.30 ± 0.44 for control, 0.1 and 1 μM, respectively). Additionally, BrdU immunofluorescence assay showed that ethosuximide-enhanced nucleus proliferation in the neuronal stem cells. Therefore, the results of this study suggest that ethosuximide may compensate damage caused by seizure attacks and possibly other neuronal loss disorders.

IntroductionBreast cancer is the primary cause of death in malignancies among females (Regulski et al., 2016). It is suggested that a major population of breast tumor was incapable of further growth but only a minute fraction was able to seed new cancers, called cancer stem cells (CSCs) (Al-Hajj et al., 2003). During recent years, studies have identified CSCs as the subpopulation of tumor cells with a unique capacity for self-renewal and the ability to give rise to a heterogeneous population of cancer cells to form tumors. Genomic instability via several gene mutations has been reported to form CSCs from normal stem cells, progenitor cells, or differentiated cells. Cancer development could be due to the fact that CSCs are associated with tumor initiation, progression, and metastasis as well as treatment resistance. Thus, CSCs have been discovered to be a suitable therapeutic target for prevention and treatment of cancer (Soltanian and Matin, 2011;Sotiropoulou et al., 2014). Breast CSCs are multiple, distinct, and nonoverlapping populations coexisting within the tumor mass (Wright et al., 2008). In 2003, breast CSCs with CD44 + /CD24 -/low / ESA + cell surface markers were isolated for the first time by Al-Hajj et al. (2003). Additionally, ALDH1, which belongs to the aldehyde dehydrogenase family, is a putative CSC marker, including breast cancer. To date, several breast cancer stem cell markers have been proposed (CD133, CD29, and CD49f), of which CD44 + /CD24 -/low and ALDH1 are used exclusively to identify these highly tumorigenic cells (Carrasco et al., 2014).The cyclooxygenase enzyme, which mediates prostaglandin production, consists of three isoforms, COX-1, COX-2, and COX-3. COX-1, a house-keeping enzyme, has a crucial role for internal homeostasis. Conversely, COX-2 is undetectable in normal tissues while it is inducible in the setting of neoplasia and inflammation (Regulski et al., 2016). COX-2 upregulation by modulating various signaling pathways can enhance production of prostaglandins, which promote tumor growth, invasion, angiogenesis, and apoptosis resistance. Recent studies have also attributed the overexpression of COX-2 to breast cancer stem-like cell (CSC-LCs) properties and cancer development (Jeong et al., 2010;Singh et al., 2011).