title: Carotenoids inhibit proliferation and regulate expression of peroxisome proliferators-activated receptor gamma (PPARγ) in K562 cancer cells.
abstract: 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 (PPARγ) plays an inhibitory role in cancer cell proliferation and growth. Involvement of PPARγ in the growth inhibition of leukemia K562 cells by carotenoids was investigated in the present study. The results demonstrated that β-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 PPARγ, partly attenuated the inhibition of K562 cell proliferation by the four carotenoids at 8μM. These carotenoids up-regulated the expression of PPARγ and p21 and down-regulated the expression of cyclin D1 in a dose-dependent manner. In addition, β-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 PPARγ 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 PPARγ expression at least partly contributed to the antiproliferative effects of β-carotene, astaxanthin, capsanthin, and bixin on K562 cells.
authors.affiliation: School of Chemical Engineering and Energy, Zhengzhou University, No. 100 Science Road, Zhengzhou 450001, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Wen-En
authors.initials: WE
authors.lastname: Zhao
authors.forename: Liqiang
authors.initials: L
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Jinyong
authors.initials: J
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051267:NF-E2-Related Factor 2; D047495:PPAR gamma; D019938:Cyclin D1; D002338:Carotenoids