Induction of p21Waf1/Cip1 by garcinol via downregulation of p38-MAPK signaling in p53-independent H1299 lung cancer

Sheng Yung Yu, Chiung Ho Liao, Ming Hsien Chien, Tsung Yu Tsai, Jen Kun Lin, Meng Shih Weng

研究成果: 雜誌貢獻文章同行評審

42 引文 斯高帕斯(Scopus)

摘要

Garcinol, a polyisoprenylated benzophenone, from Garcinia indica fruit rind has possessed anti-inflammatory, antioxidant, antiproliferation, and anticancer activities. However, the anticancer mechanisms of garcinol in lung cancer were still unclear. Therefore, we examine the effects of garcinol on antiproliferation in human lung cancer cells. Treatments with garcinol for 24 h exhibited morphological changes and inhibited the proliferation of H460 (p53-wild type) and H1299 (p53-null) cells in dose-and time-dependent manners. Furthermore, a significant G1 cell cycle arrest was observed in a dose-dependent treatment after H1299 cells were exposed in garcinol, whereas garcinol induced apoptosis rather than cell cycle arrest in H460 cells. Moreover, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), cyclin D1, and cyclin D3 were decreased, although cyclin E and cyclin-dependent kinase 6 (CDK6) were increased in garcinol-treated H1299 cells. Meanwhile, the protein levels of CDK inhibitors p21Waf1/Cip1 and p27KIP1 also exhibited upregulation after garcinol treatments. The enhanced protein-associated level between p21Waf1/Cip1 and CDK4/2 rather than p27KIP1 and CDK4/2 was demonstrated in garcinol-treated cells. Additionally, knock-down p21Waf1/Cip1 by specific siRNA competently prevented garcinol-induced G1 arrest. Besides, garcinol also inhibited ERK and p38-MAPK activations in time-dependent mode. The pretreatment with p38-MAPK inhibitor but not ERK inhibitor raised garcinol-induced G1 population cells. Co-treatment with p38-MAPK inhibitor and garcinol synergistically elevated cyclin E, p21Waf1/Cip1, and p27Kip1 expressions. Meanwhile, overexpression dominant negative p38-MAPK also enhanced garcinol-induced p21Waf1/Cip1 expression in H1299 cells. Accordingly, our data suggested that garcinol induced G1 cell cycle arrest and apoptosis in lung cancer cells under different p53 statuses. The p53-independent G1 cell cycle arrest induced by garcinol might be through upregulation of p21 Waf1/Cip1 triggered from p38-MAPK signaling inactivation.
原文英語
頁(從 - 到)2085-2095
頁數11
期刊Journal of Agricultural and Food Chemistry
62
發行號9
DOIs
出版狀態已發佈 - 三月 5 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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