| Summary: | Overcoming drug resistance and specifically targeting cancer stem cells (CSCs) are critical challenges in improving cancer therapy. Nowadays, the use of novel and native medicinal plants can provide new sources for further investigations for this purpose. The aim of this study was to assess the potential of <i>S. bachtiarica</i>, an endemic plant with diverse medicinal applications, in suppressing and targeting cancer and cancer stem cells in glioblastoma and breast cancer. The effect of <i>S. bachtiarica</i> on viability, migration, invasion, and clonogenic potential of MDAMB-231 and U87-MG cells was assessed in both two- and three-dimensional cell culture models. Additionally, we evaluated its effects on the self-renewal capacity of mammospheres. The experimental outcomes indicated that <i>S. bachtiarica</i> decreased the viability and growth rate of cells and spheroids by inducing apoptosis and inhibited colony formation, migration, and invasion of cells and spheroids. Additionally, colony and sphere-forming ability, as well as the expression of genes associated with EMT and stemness were reduced in mammospheres treated with <i>S. bachtiarica</i>. In conclusion, this study provided valuable insights into the anti-cancer effects of <i>S. bachtiarica</i>, particularly in relation to breast CSCs. Therefore, <i>S. bachtiarica</i> may be a potential adjuvant for the treatment of cancer.
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