Dawei Zhao1, Di Wu2, Gengyue Zhang3, Yongqi Li2, Weiguo Shi4, Bohua Zhong4, Hong Yu5. 1. Department of Breast Tumor, Jilin Cancer Hospital, No.1018 Hu-Guang Road, Changchun, 130012, China. 2. Tumor Center of Jilin University No.1 Hospital, No.71 Xin-Min Street, Changchun, 130021, China. 3. Cell Biology Laboratory, Jilin Province Tumor Institute, Jilin Cancer Hospital, No.1018 Hu-Guang Road, Changchun, 130012, China. 4. Institute of Pharmacology and Toxicology Academy of Military Medical Sciences, No.27 Tai-Ping Road, Beijing, 100850, China. 5. Cell Biology Laboratory, Jilin Province Tumor Institute, Jilin Cancer Hospital, No.1018 Hu-Guang Road, Changchun, 130012, China. yhzhlyy@126.com.
Abstract
PURPOSE: Irinotecan (CPT-11) is a camptothecin derivative whose potent anti-tumor activity depends on the rapid formation of an in vivo active metabolite, SN38 (7-ethyl-10-hydroxycamptothecin). CPT-11 combine with other agents are often the treatment of choice for patients with advanced or metastatic colorectal cancer (CRC). This study evaluates the cytotoxic mechanism of a novel CPT-11 derivative, ZBH-1207 in CRC cells in vitro. METHODS: The anti-proliferation effect of ZBH-1207 on tumor cells was assessed by MTT assay. The inhibition of TOP1, the alteration of cell cycle and apoptosis, and the expression of caspase-3 and PARP in CRC cells induced by ZBH-1207 were detected by DNA relaxation assay, flow cytometry, and Western blot, respectively. RESULTS: ZBH-1207 significantly inhibits the proliferation of seven tumor cell lines and retains the activity of TOP1 as compared with CPT-11. Treatment with ZBH-1207 results in more apparent cell cycle arrests and apoptosis of CRC cells than that of CPT-11 and SN38. Accordingly, up-regulation of active caspase-3 and PARP expression were relatively higher in ZBH-1207 group than that in CPT-11 and SN38 group. CONCLUSION: ZBH-1207 has higher cytotoxicity than CPT-11/SN38 in CRC cells. Its molecular mechanism involves apoptosis signaling pathway.
PURPOSE: Irinotecan (CPT-11) is a camptothecin derivative whose potent anti-tumor activity depends on the rapid formation of an in vivo active metabolite, SN38 (7-ethyl-10-hydroxycamptothecin). CPT-11 combine with other agents are often the treatment of choice for patients with advanced or metastatic colorectal cancer (CRC). This study evaluates the cytotoxic mechanism of a novel CPT-11 derivative, ZBH-1207 in CRC cells in vitro. METHODS: The anti-proliferation effect of ZBH-1207 on tumor cells was assessed by MTT assay. The inhibition of TOP1, the alteration of cell cycle and apoptosis, and the expression of caspase-3 and PARP in CRC cells induced by ZBH-1207 were detected by DNA relaxation assay, flow cytometry, and Western blot, respectively. RESULTS: ZBH-1207 significantly inhibits the proliferation of seven tumor cell lines and retains the activity of TOP1 as compared with CPT-11. Treatment with ZBH-1207 results in more apparent cell cycle arrests and apoptosis of CRC cells than that of CPT-11 and SN38. Accordingly, up-regulation of active caspase-3 and PARP expression were relatively higher in ZBH-1207 group than that in CPT-11 and SN38 group. CONCLUSION: ZBH-1207 has higher cytotoxicity than CPT-11/SN38 in CRC cells. Its molecular mechanism involves apoptosis signaling pathway.
Authors: K Takasuna; T Hagiwara; K Watanabe; S Onose; S Yoshida; E Kumazawa; E Nagai; T Kamataki Journal: Cancer Chemother Pharmacol Date: 2006-01-25 Impact factor: 3.333
Authors: A H Ko; M A Tempero; Y-S Shan; W-C Su; Y-L Lin; E Dito; A Ong; Y-W Wang; C G Yeh; L-T Chen Journal: Br J Cancer Date: 2013-07-23 Impact factor: 7.640
Authors: Sun-Ok Kim; Krisada Sakchaisri; N R Thimmegowda; Thimmegowda N R; Nak Kyun Soung; Jae-Hyuk Jang; Young Sang Kim; Kyung Sang Lee; Yong Tae Kwon; Yukihiro Asami; Jong Seog Ahn; Raymond Leo Erikson; Bo Yeon Kim Journal: PLoS One Date: 2013-01-22 Impact factor: 3.240