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

doi:10.5246/jcps.2014.09.078

Abstract

Abstract:

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

CLC Number:

R915

Supporting:

Wanwan Ma, Shunan Tang, Mingnan Cao, Zemei Ge, Runtao Li, Siwang Yu . IC5, a dithiocarbamate derivative, inhibits colon cancer cell proliferation in vitro and colitis-associated colorectal carcinogenesis in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(9): 610-616.

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