title: Thioridazine elicits potent antitumor effects in colorectal cancer stem cells.
abstract: As a member of the phenothiazine family, thioridazine (THIO) is a potent anti-anxiety and anti-psychotic drug. Recent studies have reported that THIO could suppress the growth of several types of cancer cells. However, the effect of THIO on colorectal cancer stem cells (CSCs) has not been investigated. In the present study, we examined the effect of THIO on viability of CSCs isolated from the human colon cancer cell line HCT116 and its colony-formation ability, along with its stem cell-specific gene expression. The CSCs, EpCAM+ and CD44+ subpopulations from HCT116 cells were isolated using immunomagnetic beads. After incubation with several concentrations of THIO, we evaluated the proliferation and invasion ability of colon CSCs, as well as cell apoptosis. We found that THIO significantly suppressed the proliferation and invasion of colon CSCs and induced cell apoptosis in a concentration-dependent manner. The expression of some apoptosis genes (Bax and caspase-3) was upregulated after treatment with THIO, while that of the anti-apoptosis gene Bcl-2 was downregulated. Moreover, the CSC mitochondrial membrane potential was downregulated. Overall, this study showed that THIO inhibits the proliferation of CSCs derived from the HCT116 cell line through induction of apoptosis, and thus, could be a promising agent for the treatment of colon cancer and worthy of exploring in prospective clinical studies.
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yulai
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D013881:Thioridazine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013881:Thioridazine