title: K252a inhibits proliferation of ovarian cancer cells by upregulating p21WAF1.
abstract: The furanosylated indolocarbazole, K252a, belongs to a family of microbial alkaloids that also includes staurosporine, which is known to inhibit proliferation, stimulate apoptosis and induce cell cycle arrest of cancer cells. To elucidate the involvement of K252a in ovarian cancer, we investigated the effects of K252a on the ovarian cancer cell line, SK-OV-3. SK-OV-3 cells were treated with K252a, and its effect on cell growth, cell cycle, and related measurements was assessed. MTT assays showed that the ovarian cancer cell line SK-OV-3 cells were sensitive to the growth inhibitory effect of K252a. Cell cycle analysis indicated that their exposure to K252a decreased the proportion of cells in the S-phase and increased the proportion of cells in the G0/G1 phase of the cell cycle. This occurred in concert with altered expression of p21WAF1 protein related to the G0/G1 phase of the cell cycle. These results raise the possibility that K252a may prove particularly effective in treatment of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan. takai@med.oita-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takai
authors.forename: Tami
authors.initials: T
authors.lastname: Ueda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nishida
authors.forename: Kaei
authors.initials: K
authors.lastname: Nasu
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fukuda
authors.forename: Isao
authors.initials: I
authors.lastname: Miyakawa
mesh_terms: D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D026121:Indole Alkaloids; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C493956:CDKN1A protein, human; D002227:Carbazoles; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D011493:Protein Kinase C