title: Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells.
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.
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia. amira_z12@yahoo.com.
authors.forename: Amirah Abdul
authors.initials: AA
authors.lastname: Rahman
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia.
authors.forename: Rahman
authors.initials: R
authors.lastname: Jamal
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia.
authors.forename: Roslan
authors.initials: R
authors.lastname: Harun
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia.
authors.forename: Norfilza
authors.initials: N
authors.lastname: Mokhtar
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia. wanzurinah@ppukm.ukm.edu.my.
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002396:Catechols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005233:Fatty Alcohols / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D024508:Tocotrienols / Q000008:administration & dosage*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D024508:Tocotrienols; D002392:Catechin; C007845:gingerol; C045651:epigallocatechin gallate