K252a is highly effective in suppressing the growth of human endometrial cancer cells, but has little effect on normal human endometrial epithelial cells.
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 the cell cycle arrest of cancer cells. To elucidate the involvement of K252a in endometrial cancer, we investigated the effects of K252a on three endometrial cancer cell lines. Endometrial cancer cells were treated with K252a and its effect on cell growth, cell cycle and related measurements was assessed. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that the endometrial cancer cell lines were sensitive to the growth inhibitory effect of K252a, although normal endometrial epithelial cells were viable after treatment with the same doses of K252a that induced the growth inhibition of endometrial cancer cells. 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. TUNEL assays demonstrated that K252a induced apoptosis. This occurred in concert with an altered expression of p21WAF1 and bcl-2 proteins related to the G0/G1 phase of the cell cycle and apoptosis. These results raise the possibility that K252a may prove to be particularly effective in the treatment of endometrial cancers.
Takai
Noriyuki
N
Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita 879-5593, Japan. takai@med.oita-u.ac.jp
Ueda
Tami
T
Nishida
Masakazu
M
Nasu
Kaei
K
Narahara
Hisashi
H
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002227:Carbazoles; D050759:Cyclin-Dependent Kinase Inhibitor p21; D026121:Indole Alkaloids; C049985:staurosporine aglycone