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.
Highlights
The search for chemopreventive compounds of plant origin for the development of drugs or adjuvants in the treatment of cancer
Most of the reported studies on inhibitory effects of bioactive compounds involved the use of chemo-preventive agents which have limited bioavailability while higher doses can sometimes lead to increased toxicity
MTS assays of individual 6G and γ-T3 were carried out on both HT-29 and SW837 cells at concentrations ranging from 0 to 300 μg/mL for 6G and 0 to 150 μg/mL for γ-T3. Both compounds caused a concentration-dependent decrease in cell viability in HT-29 and SW837 cells (Figure 1)
Summary
The search for chemopreventive compounds of plant origin for the development of drugs or adjuvants in the treatment of cancer. Curcumin has been shown to sensitize tumor cells and act in first line chemotherapy and radiotheraphy due to its bioavailability in the human body and it exerts its therapeutic effect at minimum concentrations in blood serum [4]. Most of the reported studies on inhibitory effects of bioactive compounds involved the use of chemo-preventive agents which have limited bioavailability while higher doses can sometimes lead to increased toxicity. The use of a combination of low concentrations of preventive agents, or multi targeted approaches has been suggested to reduce toxicity and improve efficacy of the treatment [13,14,15,16]. Objective of the present study was to determine the effect of γ-tocotrienol and 6-gingerol individually and in combination on human colorectal cancer cells
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