title: NSC606985 induces apoptosis, exerts synergistic effects with cisplatin, and inhibits hypoxia-stabilized HIF-1alpha protein in human ovarian cancer cells.
abstract: 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.
authors.affiliation: Dept. of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Dept. of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Dept. of Medicine/Endocrinology, Weill Medical College of Cornell University, New York, NY, 10021, USA.
authors.forename: Yuanshan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: Chengq@shsmu.edu.cn.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Dept. of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China. Electronic address: diwen163@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Di