Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells

  • Authors:
    • Hyun Sook Lim
    • Yong Jung Kang
    • Bokyung Sung
    • Seon Hee Kim
    • Min Jeong Kim
    • Hye Rim Kim
    • Seong Jin Kim
    • Yung Hyun Choi
    • Hyung Ryong Moon
    • Hae Young Chung
    • Nam Deuk Kim
  • View Affiliations

  • Published online on: August 19, 2015     https://doi.org/10.3892/or.2015.4208
  • Pages: 2431-2438
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Abstract

The anticancer properties of MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, in various human cancer cell lines have been previously reported. The aim of the present study was to investigate the activities of MHY-449 on human lung cancer cells in order to elucidate its underlying molecular mechanisms of action. The result showed that MHY-449 treatment inhibited cell growth in a time- and concentration‑dependent manner. Specifically, MHY-449 induced cell cycle arrest at the S phase, and the resulting increased sub-G1 fraction led to the induction of apoptosis, as determined by flow cytometric analysis and DNA fragmentation. In addition, MHY-449 was shown to induce alterations in the ratio of Bax/Bcl-2 protein expression, and contribute to the loss of mitochondrial membrane potential. These cellular events then triggered the caspase cascade and subsequent poly(ADP‑ribose) polymerase cleavage. The apoptotic cell death induced by MHY-449 was inhibited by pretreatment with Z-VAD‑FMK, a pan-caspase inhibitor. Moreover, MHY-449 downregulated the phosphorylation of Akt, and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Taken together, the results suggested that MHY-449 exerts anticancer effects by promoting cell cycle arrest and apoptosis via the downregulation of Akt. Based on these data, MHY-449 serves as a potential candidate in the chemoprevention and/or treatment of lung cancer.
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November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lim HS, Kang YJ, Sung B, Kim SH, Kim MJ, Kim HR, Kim SJ, Choi YH, Moon HR, Chung HY, Chung HY, et al: Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells. Oncol Rep 34: 2431-2438, 2015.
APA
Lim, H.S., Kang, Y.J., Sung, B., Kim, S.H., Kim, M.J., Kim, H.R. ... Kim, N.D. (2015). Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells. Oncology Reports, 34, 2431-2438. https://doi.org/10.3892/or.2015.4208
MLA
Lim, H. S., Kang, Y. J., Sung, B., Kim, S. H., Kim, M. J., Kim, H. R., Kim, S. J., Choi, Y. H., Moon, H. R., Chung, H. Y., Kim, N. D."Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells". Oncology Reports 34.5 (2015): 2431-2438.
Chicago
Lim, H. S., Kang, Y. J., Sung, B., Kim, S. H., Kim, M. J., Kim, H. R., Kim, S. J., Choi, Y. H., Moon, H. R., Chung, H. Y., Kim, N. D."Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells". Oncology Reports 34, no. 5 (2015): 2431-2438. https://doi.org/10.3892/or.2015.4208