School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Molecules. 2021 Apr 21;26(9):2422. doi: 10.3390/molecules26092422.
Cytotoxicity and apoptosis-inducing properties of compounds isolated from leaves were investigated. The hexane-soluble portion of MeOH extracts of leaves that showed cytotoxic activity was separated to yield seven compounds -. Chemical structure analysis using NMR spectroscopy and mass spectrometry confirmed that compound was canophyllol, and compounds - were garcinielliptones N, O, J, G, F, and garcinielliptin oxide, respectively. Among them, garcinielliptone G () 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 () 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 () can induce both caspase-3 activation and caspase-independent apoptosis. Therefore, garcinielliptone G () may be a potential candidate for acute leukemia treatment.
从叶片中分离得到的化合物的细胞毒性和诱导细胞凋亡特性进行了研究。对显示细胞毒性的叶片甲醇提取物的正己烷可溶部分进行分离，得到七种化合物 - 。使用 NMR 光谱和质谱进行的化学结构分析证实，化合物 为坎非醇，而化合物 - 分别为藤黄内酯 N、O、J、G、F 和藤黄内酯氧化物。其中，藤黄内酯 G () 通过诱导源自人急性单核细胞白血病和 T 淋巴细胞的 THP-1 和 Jurkat 细胞发生凋亡，表现出生长抑制作用。藤黄内酯 G () 诱导的细胞凋亡通过用荧光素标记的 Annexin V 检测早期凋亡细胞和增加 cleaved caspase-3 和 cleaved PARP 蛋白水平来证明。然而，加入 caspase 抑制剂 Z-VAD-FMK 并不影响生长抑制或细胞凋亡诱导。这些结果表明，藤黄内酯 G () 可诱导 caspase-3 激活和 caspase 非依赖性细胞凋亡。因此，藤黄内酯 G () 可能是治疗急性白血病的潜在候选药物。
