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	Noriyuki Takai, Tami Ueda, Masakazu Nishida, Kaei Nasu, Junichiro Fukuda, Isao Miyakawa
Journal	Oncology reports (Oncol Rep) Vol. 14 Issue 1 Pg. 141-3 (Jul 2005) ISSN: 1021-335X [Print] Greece
PMID	15944781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CDKN1A protein, human Carbazoles Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Enzyme Inhibitors Indole Alkaloids staurosporine aglycone Protein Kinase C
Topics	Blotting, Western Carbazoles (pharmacology) Cell Cycle (drug effects) Cell Cycle Proteins (metabolism) Cell Line, Tumor Cell Proliferation (drug effects) Cell Survival (drug effects) Cyclin-Dependent Kinase Inhibitor p21 Dose-Response Relationship, Drug Enzyme Inhibitors (pharmacology) Female Humans Indole Alkaloids Ovarian Neoplasms (metabolism, pathology) Protein Kinase C (antagonists & inhibitors) Up-Regulation (drug effects)

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