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.

Source:
courtesy of NATURALNEWS

by Evangelyn Rodriguez

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