Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway

  • Authors:
    • Su Bog Yee
    • Hye Joung Choi
    • Sang Woon Chung
    • Dong Heun Park
    • Bokyung Sung
    • Hae Young Chung
    • Nam Deuk Kim
  • View Affiliations

  • Published online on: June 18, 2015     https://doi.org/10.3892/ijo.2015.3053
  • Pages: 747-754
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Abstract

Flavonoids, a class of natural polyphenolic compounds, inhibit cell cycle progression and induce apoptosis. This study was performed to investigate the antiproliferative effect of luteolin, the flavonoid isolated from Ixeris sonchifolia Hance, and to elucidate the detailed apoptotic mechanism in HCC cells. According to the result of MTT assay luteolin possessed antiproliferative effect, and HepG2 cells were the most sensitive to luteolin. Propidium iodide staining, fluorescence activated cell sorting analysis, western blot analysis and RT-PCR were applied to compare the difference of apoptotic event between the two HCC cell lines, with wild-type p53 (HepG2) or not (Hep3B) based on time and concentration. The treatment of luteolin upregulated the expression levels of transforming growth factor β1 (TGF‑β1), p21WAF1/CIP1, p27KIP1, Smad4, and Fas in HCC cells. Thus, the expression of p21WAF1/CIP1 was controlled by another factor, such as TGF‑β1 in addition to p53, and notably the key factor might be p21WAF1/CIP1 in the remarkable switch to G1 cell cycle arrest in HepG2 cells rather than p27KIP1. Luteolin induced apoptotic cell death in Hep3B cells while caused G1 arrest in HepG2 cells. Taken together, we conclude that luteolin induces apoptosis from G1 arrest via three signaling pathways of TGF‑β1, p53, and Fas/Fas-ligand in HCC cells.
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August-2015
Volume 47 Issue 2

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

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Spandidos Publications style
Yee SB, Choi HJ, Chung SW, Park DH, Sung B, Chung HY and Kim ND: Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway. Int J Oncol 47: 747-754, 2015
APA
Yee, S.B., Choi, H.J., Chung, S.W., Park, D.H., Sung, B., Chung, H.Y., & Kim, N.D. (2015). Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway. International Journal of Oncology, 47, 747-754. https://doi.org/10.3892/ijo.2015.3053
MLA
Yee, S. B., Choi, H. J., Chung, S. W., Park, D. H., Sung, B., Chung, H. Y., Kim, N. D."Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway". International Journal of Oncology 47.2 (2015): 747-754.
Chicago
Yee, S. B., Choi, H. J., Chung, S. W., Park, D. H., Sung, B., Chung, H. Y., Kim, N. D."Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway". International Journal of Oncology 47, no. 2 (2015): 747-754. https://doi.org/10.3892/ijo.2015.3053