Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor gamma.
Glioma remains one of the most lethal human tumors in spite of the progress in radiotherapy, chemotherapy, and surgical techniques. Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. However, the mechanism remains unclear. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors (NHRs) which are involved in cellular differentiation and proliferation. In this study, we investigated if CDA-2 induced differentiation of SWO-38 glioma cells is mediated by PPARgamma. CDA-2 induced differentiation of SWO-38 cells was characterized by typical morphological changes, increased expression of GFAP, inhibition of proliferation and G(0)/G(1) cell cycle arrest. CDA-2 also triggered up-regulation of PPARgamma, GFAP and PTEN protein and a reduction of COX-2 protein. However, the effects of CDA-2 on SWO-38 cells could be partly reversed by GW9662, an irreversible PPARgamma antagonist. Our investigation demonstrated that CDA-2 could be a potential drug for tumor differentiation therapy, and activation of the PPARgamma pathway might be a crucial factor in glioma differentiation induced by CDA-2.
Lin
Chen Li
CL
Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China.
Wang
Ming Hua
MH
Department of Pathology, Hainan Medical College, Hainan, 571101, China.
Qin
Yan Fang
YF
Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China.
Fang
Mao
M
Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China.
Xie
Bin Bin
BB
Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China.
Zhong
Xue Yun
XY
Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China. tzxy@jnu.edu.cn.
D000704:Analysis of Variance; D000813:Anilides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005434:Flow Cytometry / Q000379:methods; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology*; D013997:Time Factors
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D010455:Peptides; D010648:Phenylacetates; C480340:cell differentiation agent II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human