title: Induction of G2/M phase arrest and apoptosis by potent antitumor APCA in human cervix carcinoma cells.
abstract: 3-(dimethylamino-ethylamino)-8-oxo-8H-acenaphthol[1, 2-b]pyrrole-9-carboxylic acid (APCA), as a potent antitumor compound, showed anticancer activity on a series of established cancer cells. Meanwhile, the cytotoxic effects of APCA were much smaller on normal human cells than that on cancer cells. This study investigated the molecular mechanisms underlying APCA-induced growth inhibition in HeLa cells. The results showed that the APCA-induced cell cycle arrest at G(2)/M phase correlated with cyclinB1 and cyclin-dependent kinase 1 expression downregulation in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes and increased apoptotic sub-G(1) population. Furthermore, translocation inhibition of nuclear factor-κB, upregulation of Bax, and downregulation of Bcl-2, caspase-3 and caspase-9 activation, and poly-(ADP-ribose) polymerase cleavage were observed in HeLa cells treated with APCA, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, APCA displayed an antitumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that APCA might have therapeutic potential against cervix carcinoma as an effective lead compound.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xie
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
mesh_terms: D000073:Acenaphthenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D059447:Cell Cycle Checkpoints; D002455:Cell Division / Q000187:drug effects*; D019926:Cyclin B / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D011758:Pyrroles / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C569689:3-(dimethylamino-ethylamino)-8-oxo-8H-acenaphthol(1,2-b)pyrrole-9-carboxylic acid; D000073:Acenaphthenes; D000970:Antineoplastic Agents; D019926:Cyclin B; D011758:Pyrroles; D016203:CDC2 Protein Kinase