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Article

Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor

  • Authors:
    • Sun-Mi Yun
    • Ju-Hee Lee
    • Kyung Hee Jung
    • Hyunseung Lee
    • Soyoung Lee
    • Sungwoo Hong
    • Soon-Sun Hong
  • View Affiliations / Copyright

    Affiliations: College of Medicine, Inha University, Jung-gu, Incheon 400-712, Republic of Korea, Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea
  • Pages: 201-209
    |
    Published online on: April 22, 2013
       https://doi.org/10.3892/ijo.2013.1912
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Abstract

The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in cell proliferation and survival in human cancer and is emerging as an attractive therapeutic target. In this study, we synthesized a novel PI3Kα inhibitor, HS-159 [N-(5-(3-(3-cyanophenyl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide] and evaluated its anticancer effects on Huh-7 human hepatocellular carcinoma (HCC) cells. HS-159 effectively inhibited the phosphorylation of downstream PI3K effectors such as Akt, mTOR and P70S6 kinases in a dose-dependent manner. This compound also induced apoptosis and increased the fraction of apoptotic cells in the sub-G1 phase as well as the levels of cleaved PARP, caspase-3 and -9. Furthermore, HS-159 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor which play important roles in angiogenesis. The anti-angiogenic effect of HS-159 was confirmed by the suppression of tube formation and migration of human umbilical vein endothelial cells in vitro. Collectively, our results demonstrate that HS-159 exhibited anticancer activities including the induction of apoptosis and inhibition of angiogenesis by blocking the PI3K/Akt pathway in Huh-7 cells. Therefore, we suggest that this drug may be potentially used for targeted HCC therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Yun S, Lee J, Jung KH, Lee H, Lee S, Hong S and Hong S: Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor. Int J Oncol 43: 201-209, 2013.
APA
Yun, S., Lee, J., Jung, K.H., Lee, H., Lee, S., Hong, S., & Hong, S. (2013). Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor. International Journal of Oncology, 43, 201-209. https://doi.org/10.3892/ijo.2013.1912
MLA
Yun, S., Lee, J., Jung, K. H., Lee, H., Lee, S., Hong, S., Hong, S."Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor". International Journal of Oncology 43.1 (2013): 201-209.
Chicago
Yun, S., Lee, J., Jung, K. H., Lee, H., Lee, S., Hong, S., Hong, S."Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor". International Journal of Oncology 43, no. 1 (2013): 201-209. https://doi.org/10.3892/ijo.2013.1912
Copy and paste a formatted citation
x
Spandidos Publications style
Yun S, Lee J, Jung KH, Lee H, Lee S, Hong S and Hong S: Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor. Int J Oncol 43: 201-209, 2013.
APA
Yun, S., Lee, J., Jung, K.H., Lee, H., Lee, S., Hong, S., & Hong, S. (2013). Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor. International Journal of Oncology, 43, 201-209. https://doi.org/10.3892/ijo.2013.1912
MLA
Yun, S., Lee, J., Jung, K. H., Lee, H., Lee, S., Hong, S., Hong, S."Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor". International Journal of Oncology 43.1 (2013): 201-209.
Chicago
Yun, S., Lee, J., Jung, K. H., Lee, H., Lee, S., Hong, S., Hong, S."Induction of apoptosis and suppression of angiogenesis of hepatocellular carcinoma by HS-159, a novel phosphatidylinositol 3-kinase inhibitor". International Journal of Oncology 43, no. 1 (2013): 201-209. https://doi.org/10.3892/ijo.2013.1912
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