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[摘要]：As one of the main micronutrients in vegetables and fruit carotenoids are almost daily intaken in significant quantity. Although the pharmacological roles of carotenoids in the prevention and reduction of cancer incidence have received more and more attention, the exact molecular mechanisms underlying anticancer effects of carotenoids remain unclear yet. Activated peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an inhibitory role in cancer cell proliferation and growth. Involvement of PPAR gamma in the growth inhibition of leukemia K562 cells by carotenoids was investigated in the present study. The results demonstrated that beta-carotene, astaxanthin, capsanthin, and bixin inhibited the proliferation and decreased the viability of leukemia K562 cells in dose- and time-dependent manners, induced cell apoptosis, and interfered with cell cycle progression. Pretreatment with GW9662, a potent antagonist of PPAR gamma, partly attenuated the inhibition of K562 cell proliferation by the four carotenoids at 8 mu M. These carotenoids up-regulated the expression of PPAR gamma and p21 and down-regulated the expression of cyclin D1 in a dose-dependent manner. In addition, beta-carotene, astaxanthin, capsanthin and bixin also up-regulated the expression of Nrf2, an important transcription factor in Keap1-Nrf2/EpRE/ARE signaling pathway. It appears to us that PPAR gamma signaling pathways and Keap1-Nrf2/EpRE/ARE signaling pathway were involved in the inhibition of K562 cell proliferation by carotenoids and the up-regulation of PPAR gamma expression at least partly contributed to the antiproliferative effects of beta-carotene, astaxanthin, capsanthin, and bixin on K562 cells. (c) 2011 Elsevier Inc. All rights reserved. |
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