title: γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells.
abstract: Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia. nisaqmy@yahoo.com.
authors.forename: Khairunnisa' Md
authors.initials: KM
authors.lastname: Yusof
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latiff, Bandar Tun Razak, Cheras 56000, Malaysia. suzanamakpol@yahoo.com.
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. rahmanj@ppukm.ukm.edu.my.
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. drroslan@ppukm.ukm.my.
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. norfilza@yahoo.co.uk.
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.|Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 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: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D002396:Catechols / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology*; D004357:Drug Synergism; D005233:Fatty Alcohols / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D009928:Organ Specificity; D015398:Signal Transduction; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D002839:Chromans; D003603:Cytotoxins; D005233:Fatty Alcohols; D014810:Vitamin E; C013649:plastochromanol 8; C007845:gingerol; D053148:Caspase 3
keywords: 6-gingerol (6G); HT-29; SW837 human colorectal cancer cells; synergistic; γ-tocotrienol (γ-T3)