Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (9): 610-616.DOI: 10.5246/jcps.2014.09.078

• Original articles • Previous Articles     Next Articles

IC5, a dithiocarbamate derivative, inhibits colon cancer cell proliferation in vitro and colitis-associated colorectal carcinogenesis in vivo

Wanwan Ma, Shunan Tang, Mingnan Cao, Zemei Ge, Runtao Li, Siwang Yu   

  1. Department of Chemical Biology, School of Pharmaceutical Sciences Peking University Health Science Center, Beijing 100191, China
  • Received:2014-05-19 Revised:2014-06-05 Online:2014-09-23 Published:2014-06-09
  • Contact: Tel.: 86­10­82801539
  • Supported by:
    National Natural Science Foundation (Grant No. 81272468 and 21001011) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education.


Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths, and inflammatory bowel diseases and dysregulated cell proliferation play important roles in colorectal carcinogenesis. Therefore, inhibition of inflammatory signalingand cell proliferation is used as a major strategy for chemoprevention of CRC. In the present study, it was found that IC5, a dithiocarbamate derivative, could inhibit the proliferation of LoVo human colon cancer cells in a concentration-dependent manner, with an IC50 of 22μM. The anti-proliferation effect of IC5 was accompanied by a significant cell cycle arrest in G2/M phase. Further study revealed that IC5 significantly inhibited NF-κB signaling in LoVo cells, suggesting that IC5 could inhibitinflammatory responses. We then evaluated the in vivo efficacy of IC5 to inhibit colitis-associated colorectal carcinogenesis using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model. AOM/DSS treatment resulted in a CRC incidence of 58.3%, while the incidences were decreased to 37.5% and 25% in mice orally administered with 50 and 100 mg/kg IC5, respectively. In addition, IC5 also reduced the plasma levels of alanine aminotransferase and asparatate aminotransferase. Taken together, these results suggested that IC5 could prevent colitis-associated colorectal carcinogenesis, and more attention should be paid to it as a cancer chemopreventive agent in further investigation.  

Key words: Dithiocarbamate, Colorectal cancer, Colitis-associated colorectal carcinogenesis, Chemoprevention, Proliferation, NF-κB

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