title: PPARγ-dependent pathway in the growth-inhibitory effects of K562 cells by carotenoids in combination with rosiglitazone.
abstract: BACKGROUND
  Carotenoids have been found to play roles in the prevention and therapy of some cancers which PPARγ was also discovered to be involved in. The present studies were directed to determine the inhibitory effects of carotenoids in combination with rosiglitazone, a synthetic PPARγ agonist, on K562 cell proliferation and elucidate the contribution of PPARγ-dependent pathway to cell proliferation suppression.
  
  
  METHODS
  The effects of carotenoid and rosiglitazone combination on K562 cell proliferation were evaluated by trypan blue dye exclusion assay and MTT assay. When PPARγ has been inhibited by GW9662 and siRNA, cycle-related regulator expression in K562 cells treated with carotenoid and rosiglitazone combination was analyzed by Western blotting.
  
  
  RESULTS
  Rosiglitazone inhibited K562 cell proliferation and augmented the inhibitory effects of carotenoids on the cell proliferation greatly. Specific PPARγ inhibition attenuated the cell growth suppression induced by carotenoid and rosiglitazone combination. GW9662 pre-treatment attenuated the enhanced up-regulation of PPARγ expression caused by the combination treatment. Moreover, GW9662 and PPARγ siRNA also significantly attenuated the up-regulation of p21 and down-regulation of cyclin D1 caused by carotenoids and rosiglitazone.
  
  
  CONCLUSIONS
  PPARγ signaling pathway, via stimulating p21 and inhibiting cyclin D1, may play an important role in the anti-proliferative effects of carotenoid and rosiglitazone combination on K562 cells.
  
  
  CONCLUSIONS
  Carotenoids in combination with rosiglitazone are hopeful to provide attractive dietary or supplementation-based and pharmaceutical strategies to treat cancer diseases.
authors.affiliation: School of Chemical Engineering and Energy, Zhengzhou University, No. 100 Science Road, Zhengzhou 450001, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhao
authors.forename: Huihui
authors.initials: H
authors.lastname: Gu
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Li
authors.forename: Wen-En
authors.initials: WE
authors.lastname: Zhao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020014:K562 Cells; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019938:Cyclin D1; D002338:Carotenoids
keywords: Carotenoid; K562 cell; PPARγ; Rosiglitazone