Abstract
Adult T-cell leukemia/lymphoma (ATL) is a fatal malignancy caused by infection with human T-lymphotropic virus type-1 and there is no accepted curative therapy for ATL. We searched for biological active substances for the prevention and treatment of ATL from several species of herbs. The ATL cell growth-inhibitory activity and apoptosis assay showed that carnosol, which is an ingredient contained in rosemary (Rosmarinus officinalis), induced apoptosis in ATL cells. Next, to investigate the apoptosis-inducing mechanism of carnosol, we applied proteomic analysis using fluorescent two-dimensional differential gel electrophoresis and mass spectrometry. The proteomic analysis showed that the expression of reductases, enzymes in glycolytic pathway, and enzymes in pentose phosphate pathway was increased in carnosol-treated cells, compared with untreated cells. These results suggested that carnosol affected the redox status in the cells. Further, the quantitative analysis of glutathione, which plays the central role for the maintenance of intracellular redox status, indicated that carnosol caused the decrease of glutathione in the cells. Further, N-acetyl-l-cystein, which is precursor of glutathione, canceled the efficiency of carnosol. From these results, it was suggested that the apoptosis-inducing activity of carnosol in ATL cells was caused by the depletion of glutathione.
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Acknowledgments
We dedicate this work to Mr. Fumiaki Mieno (deceased, March 19, 2013), who inspired our work in protection and exploitation of intellectual property. We thank Mrs. Sachiko Tomiyama, Mr. Tokoyo Imai, and Mr. Makoto Kodama (Miyazaki Prefectural Industrial Support Foundation) for study management. This work was supported by a grant-in-aid from the Collaboration of Regional Entities for the Advancement of Technological Excellence (CREATE) from the Japan Science and Technology Agency
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Ishida, Yi., Yamasaki, M., Yukizaki, C. et al. Carnosol, rosemary ingredient, induces apoptosis in adult T-cell leukemia/lymphoma cells via glutathione depletion: proteomic approach using fluorescent two-dimensional differential gel electrophoresis. Human Cell 27, 68–77 (2014). https://doi.org/10.1007/s13577-013-0083-6
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DOI: https://doi.org/10.1007/s13577-013-0083-6