Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells

  • Authors:
    • Hye Jung Hwang
    • Yong Jung Kang
    • Mohammad Akbar Hossain
    • Dong Hwan Kim
    • Jung Yoon Jang
    • Sun Hwa Lee
    • Jeong-Hyun Yoon
    • Hyung Ryong Moon
    • Hyung Sik Kim
    • Hae Young Chung
    • Nam Deuk Kim
  • View Affiliations

  • Published online on: October 11, 2012     https://doi.org/10.3892/ijo.2012.1659
  • Pages: 2057-2064
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Abstract

Colorectal cancer (CRC) is the second most frequent cancer in men and the third most common cancer in women in Korea. In spite of the significant advances in conventional therapeutic approaches to CRC, most patients ultimately die of their disease. There is a need to develop novel preventive approaches for this malignancy. This study was carried out to investigate the anticancer effect of the diastereoisomeric compounds, MHY-449 and MHY-450, novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivatives, on HCT116 human colon cancer cells. MHY-449 exhibited more potent cytotoxicity than MHY-450, against HCT116 cells. Treatment of cells with MHY-449 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner, and inhibition of proliferation in a time-dependent manner. The induction of apoptosis was observed by decreased cell viability, DNA fragmentation, activation of protein levels involved in death receptors. Moreover, activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase and alteration in the ratio of Bax/Bcl-2 protein expression was observed. MHY-449 induced G2/M phase arrest in the cell cycle progression which was observed by flow cytometry analysis, and a decrease in the protein expression of cyclin B1 and its activating partners Cdc25c and Cdc2. MHY-449 also caused increase in the expression levels of p53, a tumor suppressor gene, and p21WAF1/CIP and p27KIP, G2/M phase inhibitors. These results suggest that MHY-449 may be a useful candidate for chemo-prevention and/or treatment of colon cancer.
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December 2012
Volume 41 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hwang HJ, Kang YJ, Hossain MA, Kim DH, Jang JY, Lee SH, Yoon J, Moon HR, Kim HS, Chung HY, Chung HY, et al: Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells. Int J Oncol 41: 2057-2064, 2012.
APA
Hwang, H.J., Kang, Y.J., Hossain, M.A., Kim, D.H., Jang, J.Y., Lee, S.H. ... Kim, N.D. (2012). Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells. International Journal of Oncology, 41, 2057-2064. https://doi.org/10.3892/ijo.2012.1659
MLA
Hwang, H. J., Kang, Y. J., Hossain, M. A., Kim, D. H., Jang, J. Y., Lee, S. H., Yoon, J., Moon, H. R., Kim, H. S., Chung, H. Y., Kim, N. D."Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells". International Journal of Oncology 41.6 (2012): 2057-2064.
Chicago
Hwang, H. J., Kang, Y. J., Hossain, M. A., Kim, D. H., Jang, J. Y., Lee, S. H., Yoon, J., Moon, H. R., Kim, H. S., Chung, H. Y., Kim, N. D."Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells". International Journal of Oncology 41, no. 6 (2012): 2057-2064. https://doi.org/10.3892/ijo.2012.1659