Institute of Biology, University of the Philippines Diliman, 1101, Quezon City, Philippines.
Department of Biology, University of San Carlos-Talamban Campus, 6000, Cebu City, Philippines.
Asian Pac J Cancer Prev. 2021 Jan 1;22(1):53-60. doi: 10.31557/APJCP.2021.22.1.53.
The genus Aglaia (Meliaceae) is an established source of many anticancer compounds. The study evaluated the leaf extracts of Aglaia loheri, a tree native to the Philippines, as potential source of anticancer compounds.
Using bioassay-guided fractionation, A. loheri leaf extract was subjected to various chromatographic techniques and step-wise application of MTT assay on human colorectal carcinoma cells, HCT116, to determine the cytotoxic fractions. The most cytotoxic HPLC isolate was structurally identified using 1D and 2D NMR and its apoptotic effect was assessed by JC-1 staining, caspase 3/7 assay and TUNEL assay.
After stepwise chromatography fractionation, an HPLC isolate, structurally identified as aglaforbesin derivative (AFD), demonstrated potent cytotoxicity against HCT116. AFD exhibited strong toxicity (IC50 = 1.13 ±0.07 µg/mL) and high selectivity on HCT116 than normal human kidney cells (HK-2). AFD-induced toxicity to HCT116 is possibly through the stimulation of the apoptotic signaling pathway via caspase 3/7 activation and DNA fragmentation independent of mitochondrial membrane depolarization.
AFD exhibited selective cytotoxicity and apoptotic activity to HCT116 and could be further developed as anticancer drug lead.
瑞香科（Meliaceae）的 Aglaia 属是许多抗癌化合物的既定来源。本研究评估了原产于菲律宾的 A. loheri 的叶提取物，作为抗癌化合物的潜在来源。
使用基于生物测定的分步分离法，对 A. loheri 叶提取物进行了各种色谱技术处理，并对人结肠直肠癌细胞 HCT116 进行了逐步 MTT 测定，以确定细胞毒性馏分。使用 1D 和 2D NMR 对最具细胞毒性的 HPLC 分离物进行结构鉴定，并通过 JC-1 染色、caspase 3/7 测定和 TUNEL 测定评估其凋亡作用。
经过分步色谱分离后，一种 HPLC 分离物，结构鉴定为 aglaforbesin 衍生物（AFD），对 HCT116 表现出强烈的细胞毒性。AFD 对 HCT116 的毒性（IC50 = 1.13 ±0.07 µg/mL）很强，选择性高于正常人类肾细胞（HK-2）。AFD 对 HCT116 的毒性可能是通过激活 caspase 3/7 并导致 DNA 片段化而不依赖于线粒体膜去极化来刺激凋亡信号通路。
AFD 对 HCT116 表现出选择性细胞毒性和凋亡活性，可进一步开发为抗癌药物先导。
