title: Desacetyluvaricin induces S phase arrest in SW480 colorectal cancer cells through superoxide overproduction.
abstract: Annonaceous acetogenins (ACGs) are a group of fatty acid-derivatives with potent anticancer effects. In the present study, we found desacetyluvaricin (Dau) exhibited notable in vitro antiproliferative effect on SW480 human colorectal carcinoma cells with IC50 value of 14 nM. The studies on the underlying mechanisms revealed that Dau inhibited the cancer cell growth through induction of S phase cell cycle arrest from 11.3% (control) to 33.2% (160 nM Dau), which was evidenced by the decreased protein expression of cyclin A Overproduction of superoxide, intracellular DNA damage, and inhibition of MEK/ERK signaling pathway, were also found involved in cells exposed to Dau. Moreover, pre-treatment of the cells with ascorbic acid significantly prevented the Dau-induced overproduction of superoxide, DNA damage and cell cycle arrest. Taken together, our results suggest that Dau induces S phase arrest in cancer cells by firstly superoxide overproduction and subsequently the involvement of various signaling pathways.
authors.affiliation: School of Life Sciences, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong S.A.R., China.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Xue
authors.forename: Guang-Xiong
authors.initials: GX
authors.lastname: Zhou
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.forename: Mei-Yuk
authors.initials: MY
authors.lastname: Choi
authors.forename: Yum-Shing
authors.initials: YS
authors.lastname: Wong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D005663:Furans / Q000008:administration & dosage; D006801:Humans; D016196:S Phase / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D005663:Furans; D013481:Superoxides; C046853:desacetyluvaricin
keywords: ANNONACEOUS ACETOGENIN; CANCER CHEMOPREVENTION; DESACETYLUVARICIN; S PHASE ARREST; SUPEROXIDE