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Cancer Chemotherapy and Pharmacology

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01.11.2013 | Original Article

Evaluation of resveratrol sensitivities and metabolic patterns in human and rat glioblastoma cells

verfasst von: Zheng Sun, Shun Shi, Hong Li, Xiao-Hong Shu, Xiao-Yan Chen, Qing-You Kong, Jia Liu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2013

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Abstract

Purpose

To further elucidate the correlation of resveratrol sensitivities with biotransformation activities of human and rat glioblastoma cells for personalized anti-glioblastoma therapy.

Methods

Resveratrol sensitivity of human U251 and rat RG2 and C6 glioblastoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide/MTT, flow cytometry, and TUNEL assays. The metabolic patterns of those cell lines were analyzed by high-performance liquid chromatography/HPLC coupled with tandem mass spectrum/MS/MS, and high-resolution mass spectrometry/HRMS. Immunocytochemical staining and Western blotting were employed to check resveratrol metabolic enzyme expression.

Results

Both rat RG2 and C6 and human U251 glioblastoma cells are sensitive to 100 μM resveratrol in terms of growth arrest and increased apoptotic fraction. The main resveratrol metabolite in U251 cells is monosulfate biotransformed by sulfotransferases/SULTs and in RG2 and C6 cells is monoglucuronide generated by UDP-glucuronosyltransferase/UGT. Both metabolites show lesser therapeutic efficacy. Although brain-associated UGTs (UGT1A6, 2B7, and 8) and SULTs (SULT1A1, 1C2, and 4A1) are expressed in rat and human glioma cells, the overall level of UGTs is predominant in the rat and SULTs in human glioblastoma cells. In similar to SULT expression pattern, UGT1A6, 2B7, and 8 are frequently downregulated (84.6 %, 82/97; 90.7 %, 88/97; 80.4 %, 78/97) in human glioblastoma tissues.

Conclusion

Our results suggest (1) the decreased resveratrol biotransforming activity in rat and human resveratrol-sensitive glioblastoma cells; (2) the discrepant resveratrol metabolic patterns between human and rat glioblastoma cells; (3) the more powerful anti-glioblastoma efficacy of trans-resveratrol rather than resveratrol monoglucuronide or monosulfate; and (4) the value of RG2 and C6 cells in establishing resveratrol-based rat in vivo therapeutic model.

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Titel: Evaluation of resveratrol sensitivities and metabolic patterns in human and rat glioblastoma cells
verfasst von: Zheng Sun
Shun Shi
Hong Li
Xiao-Hong Shu
Xiao-Yan Chen
Qing-You Kong
Jia Liu
Publikationsdatum: 01.11.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2274-y

Springer Medizin

Evaluation of resveratrol sensitivities and metabolic patterns in human and rat glioblastoma cells

Abstract

Purpose

Methods

Results

Conclusion

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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