Gwang Hun Park, Jae Ho Park, Hun Ji Eo, Hun Min Song, Jeong Rak Lee, Man Hyo Lee and Jin Boo Jeong
Posters: Altern Integ Med
A beliophyllum distichum Nakai ( A distichum ) has been reported to exert the inhibitory effect on angiotensin converting enzyme and aldose reductase. Recently, our group found that branch extracts from ethyl acetate fraction from branch of A. distichum (EAFAD-B) induces apoptosis through ATF3 activation in human colorectal cancer cells. However, anti- cancer reagents exert their activity through the regulation of various molecular targets. Therefore, the elucidation of potential mechanisms of EAFAD-B for anti-cancer activity may be necessary. To elucidate the potential mechanism of EAFAD-B for anti-cancer activity, we evaluated the regulation of cyclin D1 in human colorectal cancer cells. EAFAD-B decreased cellular accumulation of exogenously-induced cyclin D1 protein. However, cyclin D1 mRNA was not changed by EAFAD-B. Inhibition of proteasomal degradation by MG132 attenuated silymarin-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with EAFAD-B. In addition, EAFAD-B induced threonine-286 phosphorylation of cyclin D1 and EAFAD-B-mediated cyclin D1 proteasomal degradation was attenuated by a point mutation of threonine-286 to alanine. Inhibitions of both ERK1/2 by PD98059 and NF-κB by a selective inhibitor, BAY 11-7082 suppressed cyclin D1 downregulation by EAFAD-B. Conclusion: From these results, we suggest that EAFAD-B-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2-dependent NF-κB activation. The current study provides new mechanistic link between EAFAD-B and anti-cancer activity in human colorectal cancer cells.
Alternative & Integrative Medicine received 476 citations as per Google Scholar report
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