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Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor γ

  • Laboratory Investigation - human/animal tissue
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Abstract

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 PPARγ. CDA-2 induced differentiation of SWO-38 cells was characterized by typical morphological changes, increased expression of GFAP, inhibition of proliferation and G0/G1 cell cycle arrest. CDA-2 also triggered up-regulation of PPARγ, 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 PPARγ antagonist. Our investigation demonstrated that CDA-2 could be a potential drug for tumor differentiation therapy, and activation of the PPARγ pathway might be a crucial factor in glioma differentiation induced by CDA-2.

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Acknowledgements

This research was supported by National Natural Science Foundation of China (No. 30670795) and Natural Science Foundation of Guangdong Province, China (No. 06025208). We thank Bin Du, Kaishan Liu, Penge Zheng and Ying Zhong for excellent technical assistance and continued support of this work. We thank Everlife Pharmaceutical Co. Ltd. (Hefei, China) for providing CDA-2.

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Authors and Affiliations

  1. Department of Pathology, Medical College of Jinan University, Guangzhou, 510632, China

    Chen Li Lin, Yan Fang Qin, Mao Fang, Bin Bin Xie & Xue Yun Zhong

  2. Department of Pathology, Hainan Medical College, Hainan, 571101, China

    Ming Hua Wang

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  1. Chen Li Lin
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Correspondence to Xue Yun Zhong.

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Chen-Li Lin and Ming-Hua Wang contributed equally.

All authors have read and approved the final manuscript, Chen-Li Lin set up the protocols. Ming-Hua Wang contributed in the experimental procedures. Mao Fang and Bin-Bin Xie gave advice on the work and helped in the interpretation of the data. Xue-Yun Zhong supervised all the work and wrote the manuscript together with Chen-Li Lin and Ming-Hua Wang.

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Lin, C.L., Wang, M.H., Qin, Y.F. et al. Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor γ. J Neurooncol 95, 29–36 (2009). https://doi.org/10.1007/s11060-009-9900-x

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