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Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells
Authors:YoungSook Yun  Mariko Shioura  Yukio Hitotsuyanagi  Satoshi Yotsumoto  Yuji Takahashi  Yutaka Aoyagi  Takeshi Kinoshita  Koichi Takeya  Hideshi Inoue
Affiliation:1.School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; (M.S.); (S.Y.); (Y.T.); (H.I.);2.School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; (Y.H.); (Y.A.); (K.T.);3.Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan;
Abstract:Cytotoxicity and apoptosis-inducing properties of compounds isolated from Garcinia subelliptica leaves were investigated. The hexane-soluble portion of MeOH extracts of G. subelliptica leaves that showed cytotoxic activity was separated to yield seven compounds 1–7. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound 1 was canophyllol, and compounds 2–7 were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G (5) showed growth inhibition by causing apoptosis in THP-1 and Jurkat cells derived from human acute monocytic leukemia and T lymphocyte cells, respectively. Apoptosis induced by garcinielliptone G (5) was demonstrated by the detection of early apoptotic cells with fluorescein-labeled Annexin V and increases in cleaved caspase-3 and cleaved PARP protein levels. However, the addition of caspase inhibitor Z-VAD-FMK did not affect growth arrest or apoptosis induction. These results suggest that garcinielliptone G (5) can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G (5) may be a potential candidate for acute leukemia treatment.
Keywords:Garcinia subelliptica   garcinielliptone G   apoptosis   human acute leukemia cell lines
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