title: Inhibition of STAT3 signalling contributes to the antimelanoma action of atractylenolide II.
abstract: Our previous studies showed that atractylenolide II (AT-II) has antimelanoma effects in B16 melanoma cells. In this study, we investigated the involvement of STAT3 signalling in the antimelanoma action of AT-II. Daily administration of AT-II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a B16 xenograft mouse model and inhibited the activation/phosphorylation of STAT3 and Src in the xenografts. In B16 and A375 cells, AT-II (20, 40 μm) treatment for 48 h dose-dependently reduced protein expression levels of phospho-STAT3, phospho-Src, as well as STAT3-regulated Mcl-1 and Bcl-xL. Overexpression of a constitutively active variant of STAT3, STAT3C in A375 cells diminished the antiproliferative and apoptotic effects of AT-II. These data suggest that inhibition of STAT3 signalling contributes to the antimelanoma action of AT-II. Our findings shed new light on the mechanism of action underlying the antimelanoma effects of AT-II and provide further pharmacological basis for developing AT-II as a novel melanoma chemopreventive/chemotherapeutic agent.
authors: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors: Xiu-Qiong
authors: XQ
authors: Fu
authors: Gui-Xin
authors: GX
authors: Chou
authors: Hiu Yee
authors: HY
authors: Kwan
authors: Anfernee Kai-Wing
authors: AK
authors: Tse
authors: Li-Han
authors: LH
authors: Zhao
authors: Tsz-Kin
authors: TK
authors: Yuen
authors: Hui-Hui
authors: HH
authors: Cao
authors: Hua
authors: H
authors: Yu
authors: Xiao-Juan
authors: XJ
authors: Chao
authors: Tao
authors: T
authors: Su
authors: Brian Chi-Yan
authors: BC
authors: Cheng
authors: Xue-Gang
authors: XG
authors: Sun
authors: Zhi-Ling
authors: ZL
authors: Yu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry; D017209:Apoptosis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D007783:Lactones; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012717:Sesquiterpenes; C494087:Stat3 protein, mouse; C458582:atractylenolide II
keywords: STAT3; Src; atractylenolide II; melanoma