title: Dihydroartemisinin suppresses growth of squamous cell carcinoma A431 cells by targeting the Wnt/β-catenin pathway.
abstract: The antimalarial effects of dihydroartemisinin (DHA) have been well documented. However, its potential against skin cancer has not been explored as yet. Therefore, we assessed the function of DHA as an inhibitory factor of squamous cell carcinoma in A431 cells and the underlying mechanism was explored. After stimulation of A431 cells and Hacat cells (normal human keratinocyte cells, as control) with various doses of DHA, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of both cell lines and cell apoptosis was analyzed by flow cytometric analysis. Furthermore, after pretreatment with the Wnt/β-catenin signaling pathway activator BIO or anti-caspase-3 antibody, mRNA levels of antiapoptotic gene survivin and proapoptotic gene caspease-3 were explored by quantitative real-time PCR, the corresponding protein levels were detected by western blotting, and the proliferation of A431 cells was also analyzed. DHA inhibited the proliferation and viability of A431 cells in a time-dependent and dose-dependent manner and induced cell apoptosis. We also observed decreased surviving expression and increased caspase-3 expression of A431 cells. Furthermore, these effects depended on the suppression of Wnt/β-catenin signaling as pretreatment with the Wnt activator BIO markedly dampened the DHA-induced effects. More interestingly, when the caspase-3 expression was silenced using an antibody, the DHA-induced growth inhibition of A431 cells was offset significantly. Our results confirm that DHA inhibits skin cancer A431 cells by suppressing Wnt/β-catenin signaling. Our findings provide a potential target for squamous cell carcinoma treatment.
authors.affiliation: aDepartments of Dermatology bEndocrinology cCentral Laboratory, the Third Affiliated Hospital of Xi'an Jiaotong University dDepartment of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hai-ying
authors.initials: HY
authors.lastname: Hui
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Sheng-xiang
authors.initials: SX
authors.lastname: Xiao
authors.forename: Mei-fang
authors.initials: MF
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000077022:Survivin; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051153:Wnt Proteins; D051176:beta Catenin; C039060:artenimol; D053148:Caspase 3