The camptothecins, which target the intranuclear
enzyme topoisomerase I, have advanced to the forefront of several areas of developmental
chemotherapy of
cancers. In the present study, we investigated the potential anti-human
ovarian cancer effects of
NSC606985, a novel and rarely studied
camptothecin analog, and its combination with
cisplatin (CDDP). Human
ovarian cancer cell line COC1 cells were treated with different nanomolar of
NSC606985 with or without CDDP, and cell growth and apoptosis were evaluated, respectively, by MTT assay and
annexin-V assay on flow cytometry. Chou-Talalay analysis was used to evaluate combined effect of
NSC606985 and CDDP. Western blot was used to detect
protein kinase Cdelta (PKCdelta),
caspase-3 and
hypoxia-inducible factor-1alpha (HIF-1alpha)
proteins. Our results showed that
NSC606985 at nanomolar concentration induced apoptosis with the activation of PKCdelta in COC1 cells. Especially,
NSC606985 presented the significant combined effects on COC1 cells in terms of growth inhibition and apoptosis induction. In addition,
NSC606985 significantly antagonized the accumulation of HIF-1alpha stabilized by
hypoxia or
hypoxia-mimetic agent. These results suggest that
NSC606985 and its combination with CDDP present the therapeutic potential on
ovarian cancer, and deserve further preclinical and clinical studies.