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Molecules 2014, 19(9), 14528-14541; doi:10.3390/molecules190914528

Tocotrienol-Rich Fraction, [6]-Gingerol and Epigallocatechin Gallate Inhibit Proliferation and Induce Apoptosis of Glioma Cancer Cells

1
UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia
2
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia
*
Authors to whom correspondence should be addressed.
Received: 24 July 2014 / Revised: 26 August 2014 / Accepted: 1 September 2014 / Published: 12 September 2014
(This article belongs to the Collection Bioactive Compounds)
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Abstract

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles. View Full-Text
Keywords: tocotrienol-rich fraction; [6]-gingerol; epigallocatechin gallate; asiaticoside; synergy; glioma tocotrienol-rich fraction; [6]-gingerol; epigallocatechin gallate; asiaticoside; synergy; glioma
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MDPI and ACS Style

Rahman, A.A.; Makpol, S.; Jamal, R.; Harun, R.; Mokhtar, N.; Ngah, W.Z.W. Tocotrienol-Rich Fraction, [6]-Gingerol and Epigallocatechin Gallate Inhibit Proliferation and Induce Apoptosis of Glioma Cancer Cells. Molecules 2014, 19, 14528-14541.

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