Garcinielliptone G from Garcinia subelliptica Induces Apoptosis in Acute Leukemia Cells

亚椭圆藤黄中的 Garcinielliptone G 可诱导急性白血病细胞凋亡

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作者:YoungSook Yun, Mariko Shioura, Yukio Hitotsuyanagi, Satoshi Yotsumoto, Yuji Takahashi, Yutaka Aoyagi, Takeshi Kinoshita, Koichi Takeya, Hideshi Inoue

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.

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