The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells

Liao,Yu-Ren; Lu,Chi-Cheng; Lai,Kuang-Chi; Yang,Jai-Sing; Kuo,Sheng‑Chu; Wen,Yen-Fang; Fushiya,Shinji; Wu,Tian-Shung

doi:10.3892/mmr.2013.1359

The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells

Authors:
- Yu-Ren Liao
- Chi-Cheng Lu
- Kuang-Chi Lai
- Jai-Sing Yang
- Sheng‑Chu Kuo
- Yen-Fang Wen
- Shinji Fushiya
- Tian-Shung Wu
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Affiliations: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C., Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan, R.O.C., School of Medicine, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C., Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, R.O.C., Medicinal Chemistry Laboratory, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu 300, Taiwan, R.O.C., Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, Saitama 362-0806, Japan
Published online on: March 5, 2013 https://doi.org/10.3892/mmr.2013.1359
Pages: 1539-1544

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Abstract

We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.

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