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Background:  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.Methods:  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.Results:  After stepwise chromatography fractionation, an HPLC isolate, structurally identified as aglaforbesin derivative (AFD), demonstrated potent cytotoxicity against HCT116. AFD exhibited strong toxicity (IC 50  = 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.Conclusion:  AFD exhibited selective cytotoxicity and apoptotic activity to HCT116 and could be further developed as anticancer drug lead.

Cytotoxic and Apoptotic Activity of Aglaforbesin Derivative Isolated from Aglaia loheri Merr. on HCT116 Human Colorectal Cancer Cells