Korean Journal of Plant Resources (한국자원식물학회지)

The Plant Resources Society of Korea (한국자원식물학회)
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Silymarin-Mediated Degradation of c-Myc Contributes to the Inhibition of Cell Proliferation in Human Colorectal Cancer Cells

  • Eo, Hyun Ji (Department of Medicinal Plant Resources, Andong National University) ;
  • Jeong, Jin Boo (Department of Medicinal Plant Resources, Andong National University) ;
  • Koo, Jin Suk (Department of Medicinal Plant Resources, Andong National University) ;
  • Jeong, Hyung Jin (Department of Medicinal Plant Resources, Andong National University)
  • Received : 2016.11.15
  • Accepted : 2017.01.09
  • Published : 2017.06.30
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Abstract

In this study, we elucidated the molecular mechanism of silymarin by which silymarin may inhibits cell proliferation in human colorectal cancer cells in order to search the new potential anti-cancer target associated with the cell growth arrest. Silymarin reduced the level of c-Myc protein but not mRNA level indicating that silymarin-mediated downregulation of c-Myc may result from the proteasomal degradation. In the confirmation of silymarin-mediated c-Myc degradation, MG132 as a proteasome inhibitor attenuated c-Myc degradation by silymarin. In addition, silymarin phosphorylated the threonine-58 (Thr58) of c-Myc and the point mutation of Thr58 to alanine blocked its degradation by silymarin, which indicates that Thr58 phosphorylation may be an important modification for silymarin-mediated c-Myc degradation. We observed that the inhibition of ERK1/2, p38 and $GSK3{\beta}$ blocked the Thr58 phosphorylation and subsequent c-Myc degradation by silymarin. Finally, the point mutation of Thr58 to alanine attenuated silymarin-mediated inhibition of the cell growth. The results suggest that silymarin induces the cell growth arrest through c-Myc proteasomal degradation via ERK1/2, p38 and $GSK3{\beta}-dependent$ Thr58 phosphorylation.

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References

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