Carnosol,rosemary ingredient,induces apoptosis in adult T-cell leukemia/lymphoma cells via glutathione depletion: proteomic approach using fluorescent two-dimensional differential gel electrophoresis |
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Authors: | Yo-ichi Ishida Masao Yamasaki Chizuko Yukizaki Kazuo Nishiyama Hirohito Tsubouchi Akihiko Okayama Hiroaki Kataoka |
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Affiliation: | 1. Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan 2. Miyazaki Prefectural Industrial Support Foundation, 16500-2 Higashi-Kaminaka, Sadowara-cho, Miyazaki, 880-0303, Japan 3. Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan 4. Miyazaki Prefecture Food Research and Development Center, 16500-2 Higashi-Kaminaka, Sadowara-cho, Miyazaki, 880-0303, Japan 5. Digestive Disease and Lifestyle-related Disease Health Research, Human and Environmental Sciences, Kagoshima University Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan 6. Division of Rheumatology, Infectious Diseases, and Laboratory Medicine, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan 7. Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
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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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