Ethyl acetate extract from Glycosmis parva leaf induces apoptosis and cell-cycle arrest by decreasing expression of COX-2 and altering BCL-2 family gene expression in human colorectal cancer HT-29 cells.

Nattaporn Buranabunwong, Nijsiri Ruangrungsi, Chaisak Chansriniyom, Wacharee Limpanasithikul

Pharmaceutical biology 2015 Apr

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Glycosmis parva Craib (Rutaceae) is reported to have cytotoxic and anti-inflammatory activities by decreasing COX-2 expression. To investigate the effect of G. parva on human colorectal cancer cells expressing COX-2, HT-29 cells. HT-29 cells were treated with ethyl acetate extract from the leaves of G. parva (GPE 6.25-100 µg/ml) for 24-72 h. Cell viability was evaluated by the resuzurin reduction assay. An apoptotic study was performed using annexinV/FITC-PI staining. The cell-cycle pattern was investigated by PI staining. The expression of BCL-2 family genes was analyzed by quantitative RT-PCR and expression of cyclins and COX-2 were done by RT-PCR. GPE at 6.25-100 µg/ml reduced HT-29 cell viability with IC50 values of 69.49, 55.89, and 48.94 µg/ml at 24, 48, and 72 h, respectively. HT-29 apoptosis was induced by 18.23% at 100 µg/ml. Cells in S phase decreased by 5.22% and 13.28% at 50 and 100 µg/ml, respectively, causing G0/G1 (10.6% at 50 µg/ml) and G2/M (15.67% at 100 µg/ml) accumulation. GPE at 50 µg/ml downregulated cyclin A (11.46%), cyclin E (17.98%), BCL-2 (0.32-fold), and COX-2 (29.06%) expression with an increased BAK expression (1.79-fold). GPE reduced HT-29 cell viability, inhibited cell proliferation, induced apoptosis, and arrested the cell cycle. Underlying mechanisms may involve decreases in COX-2, cyclin A, and cyclin E expression in addition to changes in BCL-2 family gene expression. Fundamental knowledge of GPE anticancer effects found in this study could lead to future use of this compound for colorectal cancer treatment.

Citation

Nattaporn Buranabunwong, Nijsiri Ruangrungsi, Chaisak Chansriniyom, Wacharee Limpanasithikul. Ethyl acetate extract from Glycosmis parva leaf induces apoptosis and cell-cycle arrest by decreasing expression of COX-2 and altering BCL-2 family gene expression in human colorectal cancer HT-29 cells. Pharmaceutical biology. 2015 Apr;53(4):540-7