4.5 Article

A novel irinotecan derivative ZBH-1207 with different anti-tumor mechanism from CPT-11 against colon cancer cells

期刊

MOLECULAR BIOLOGY REPORTS
卷 49, 期 9, 页码 8359-8368

出版社

SPRINGER
DOI: 10.1007/s11033-022-07652-2

关键词

Irinotecan derivate; CPT-11; SN38; DNA topoisomerase I; Apoptosis; Cell cycle

资金

  1. Jilin Province health department Research Program [2012Z037]
  2. Jilin Province Science and Technology Development Application Basic Research Program [20130102097JC]
  3. Jilin Province Natural Science Foundation [20200201479JC]

向作者/读者索取更多资源

This study evaluates the cytotoxic mechanism of ZBH-1207, a novel CPT-11 derivative, in CRC cells. The results demonstrate that ZBH-1207 has significant inhibitory effects on tumor cell proliferation and induces more cell cycle arrests and apoptosis compared to CPT-11 and SN38. Thus, ZBH-1207 may have higher anti-tumor activity in CRC treatment.
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.

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