Centre for Natural Product Research and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University Malaya, 50603 Kuala Lumpur, Malaysia.
Molecules. 2010 Nov 9;15(11):8048-59. doi: 10.3390/molecules15118048.
1'-(S)-1'-Acetoxychavicol acetate (ACA) isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff. was investigated for its potential as an anticancer drug. In this communication, we describe the cytotoxic and apoptotic properties of ACA on five human tumour cell lines. Data from MTT cell viability assays indicated that ACA induced both time- and dose-dependent cytotoxicity on all tumour cell lines tested and had no adverse cytotoxic effects on normal cells. Total mortality of the entire tumour cell population was achieved within 30 hrs when treated with ACA at 40.0 µM concentration. Flow cytometric analysis for annexin-V and PI dual staining demonstrated that cell death occurred via apoptosis, followed by secondary necrosis. The apoptotic effects of ACA were confirmed via the DNA fragmentation assay, in which consistent laddering of genomic DNA was observed for all tumour cell lines after a 24 hrs post-treatment period at the IC(50) concentration of ACA. A cell cycle analysis using PI staining also demonstrated that ACA induced cell cycle arrest at the G(0)/G(1) phase, corresponding to oral tumour cell lines. In conclusion, ACA exhibits enormous potential for future development as a chemotherapeutic drug against various malignancies.
1'-(S)-1'-乙酰氧基胡椒酚乙酸酯 (ACA) 从马来西亚民族药用植物 Alpinia conchigera Griff. 中分离出来，被研究作为一种抗癌药物。在本通讯中，我们描述了 ACA 对五种人肿瘤细胞系的细胞毒性和凋亡特性。MTT 细胞活力测定数据表明，ACA 对所有测试的肿瘤细胞系均诱导时间和剂量依赖性细胞毒性，对正常细胞无不良细胞毒性作用。当用 40.0 μM 浓度的 ACA 处理时，整个肿瘤细胞群体的总死亡率在 30 小时内达到。用 Annexin-V 和 PI 双重染色的流式细胞术分析表明，细胞死亡通过凋亡发生，随后继发坏死。通过 DNA 片段化测定证实了 ACA 的凋亡作用，在用 ACA 的 IC(50)浓度处理 24 小时后，所有肿瘤细胞系均观察到一致的基因组 DNA 梯状。用 PI 染色进行的细胞周期分析也表明，ACA 诱导细胞周期停滞在 G(0)/G(1)期，与口腔肿瘤细胞系相对应。总之，ACA 具有巨大的潜力，可作为针对各种恶性肿瘤的化疗药物进行进一步开发。
