Malaysian researchers investigated the mechanisms underlying the anti-cancer effects of a combination treatment of y-tocotrienol and 6-gingerol. They reported their findings in an article published in the Journal of Natural Medicines.
- In their previous study, the researchers reported that y-tocotrienol (yT3) and 6-gingerol (6G) synergistically inhibited the proliferation of human colorectal cancer cells.
- To elucidate the mechanisms involved in this suppression, they used RNA sequencing techniques and conducted transcriptome analysis of the total RNA from both untreated and yT3 + 6G-treated SW837 cancer cells.
- High-throughput sequencing was performed at approximately 30 to 60 million coverage.
- The researchers found that changes in cancer-specific gene expression occurred in the yT3 + 6G-treated cells.
- Functional enrichment pathway analysis also suggested that the combination of yT3 and 6G modulated more than one pathway.
- yT3 + 6G interfered with the cell cycle process, downregulated the Wnt signaling pathway and induced caspase-independent apoptosis by inducing mitochondrial dysfunction, activating the endoplasmic reticulum (ER) unfolded protein response (UPR), disrupting DNA repair mechanisms and inactivating the cell cycle.
- The latter, noted the researchers, was made possible by the downregulation of proliferation-related genes like FOXM1.
- Meanwhile, yT3 + 6G exerted a cytotoxic effect by upregulating genes involved in stress response activation.
- The combination treatment also exerted cystostatic effects by downregulating the main regulator genes in the cell cycle.
- RNA sequencing and RT-qPCR results revealed that genes like ATF6, DDIT3, GADD34, FOXM1, CDK1 and p21, which are involved in stress response-, apoptosis- and proliferation-related pathways, displayed concordant patterns of gene expression.
Based on these findings, the researchers concluded that bioactive compounds like y-tocotrienol and 6-gingerol can be used to effectively suppress cancer cell growth.
Yusof KM, Makpol S, Fen LS, Jamal R, Ngah WZW. SUPPRESSION OF COLORECTAL CANCER CELL GROWTH BY COMBINED TREATMENT OF 6-GINGEROL AND ?-TOCOTRIENOL VIA ALTERATION OF MULTIPLE SIGNALLING PATHWAYS. Journal of Natural Medicines. 2019;73(4):745–760. DOI: 10.1007/s11418-019-01323-6
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