Ions of dasatinib with Pac and SN38 (Additional files 4, 5, 6 and 7). CombinedIons

Ions of dasatinib with Pac and SN38 (Additional files 4, 5, 6 and 7). Combined
Ions of dasatinib with Pac and SN38 (Additional files 4, 5, 6 and 7). Combined administrations of dasatinib withFigure 15 Effects of dasatinib and/or Eto on the proportion of ALDH1-positive cells in breast cancer cells. The Aldefluor assay demonstrated that dasatinib alone and dasatinib with Eto increased the proportion of ALDH1-positive cells in BT-474 cells.Kurebayashi et al. BMC Cancer 2010, 10:568 http://www.biomedcentral.com/1471-2407/10/Page 9 ofchemotherapeutic agents may be more useful for the treatment of breast cancers of the basal B subtype. Recent preclinical studies have suggested that a small component of tumor cells, so-called cancer stem cells play critical roles in the development, progression, metastasis and resistance to chemotherapy and radiotherapy in malignancies [28]. Interestingly, it was reported that a dual HER1/HER2 inhibitor lapatinib significantly purchase Pan-RAS-IN-1 reduced the proportion of CD44+/CD24- breast cancer cells, putative stem cells, and also reduced the number of mammosphere-forming activity associated with a significant antitumor activity in HER2-positive breast cancers in the neoadjuvant setting [13]. In contrast, cytotoxic chemotherapies including Dox increased the proportion of CD44/CD24- breast cancer cells and mammosphereforming activity associated with a significant antitumor activity in HER2-negative breast cancers [13]. Notably, a very recent study has shown that cytotoxic chemotherapies including an anthracycline and taxane increased the proportion of ALDH1-positive breast cancer cells but not that of CD44+/CD24- breast cancer cells [29]. Additionally, another preclinical study has suggested that antiHER2 monoclonal antibody trastuzumab effectively decreases the proportion of putative breast cancer stem cells in HER2-positive breast cancer cells [12]. More recently, an anti-diabetes mellitus agent metformin and 8-quinolinol have been reported PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27107493 to effectively target breast cancer stem cells and synergistically inhibit tumor growth together with the chemotherapeutic agents Dox and Pac, respectively [30]. These emerging preclinical data suggest that a combined use of anti-stem cell agents with chemotherapeutic agents might provide a longer tumor regression as well as cure for patients with malignancies. To investigate the effects of dasatinib and Eto on breast cancer stem cells, the proportion of ALDH1-positive cells was examined before and after the treatments with these agents using immunocytochemistry and Aldefluor assay. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in breast cancer cell lines of the basal B subtype, which were highly sensitive to dasatinib. In contrast, dasatinib significantly increased the proportion of ALDH1-positive cells in the BT-474 cell line, which was categorized as the luminal B subtype and insensitive to dasatinib. A cytotoxic agent Eto did not significantly decrease the proportion of ALDH1-positive cells in breast cancer cell lines of either luminal B or basal B subtypes (Figures 10, 11 and 12). These findings strongly suggest for the first time that the Src inhibitor dasatinib preferentially decreased the proportion of ALDH1positive, putative breast cancer stem cells in breast cancer cells of the basal B subtype. However, mechanisms of action responsible for the anti-stem cell activity of dasatinib still remain to be elucidated. A recent preclinical study indicated that ablation of focal adhesion kinase (FAK)reduces the proportion of.