Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer

Hong,Sang-Won; Jung,Kyung  Hee; Choi,Myung-Joo; Kim,Da  Young; Lee,Hee‑Seung; Zheng,Hong-Mei; Li,Guang  Yong; El‑Deeb,Ibrahim  M.; Park,Byung  Sun; Lee,So   Ha; Hong,Soon-Sun

doi:10.3892/ijo.2012.1609

Anticancer effects of KI-10F: A novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer

Authors:
- Sang-Won Hong
- Kyung Hee Jung
- Myung-Joo Choi
- Da Young Kim
- Hee‑Seung Lee
- Hong-Mei Zheng
- Guang Yong Li
- Ibrahim M. El‑Deeb
- Byung Sun Park
- So Ha Lee
- Soon-Sun Hong
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Affiliations: NCEED and Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea, Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 130-650, Republic of Korea
Published online on: August 27, 2012 https://doi.org/10.3892/ijo.2012.1609
Pages: 1715-1722

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Abstract

The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino) phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl) was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth of human colon cancer cells and induced apoptosis by increasing the proportion of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC tube formation and migration showed that KI-10F effectively inhibited the angiogenesis process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F produced a stronger antitumor activity than 5-FU, a conventional anticancer drug prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry using isolated tumor tissue samples. Taken together, our results demonstrated that KI-10F induces apoptosis and inhibits cell growth and angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective chemotherapeutic candidate for use against colon cancer.

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