Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways

This study aimed to identify and elucidate molecular mechanisms involved in the suppression of SW837 colorectal cancer cells modulated by combined tre atment of γ-tocotrienol and 6-gingerol. Total RNA from both untreated and treated cells was prepared for transcriptome analysis using RNA sequencing techniques. We performed high-throughput sequencing at approximately 30–60 million coverage on both untreated and 6G + γT3-treated cells. The results showed that cancer-specific differential gene expression occurred and functional enrichment pathway analysis suggested that more than one pathway was modulated in 6G + γT3-treated cells. Combined treatment with 6G + γT3 augmented its chemotherapeutic effect by interfering with the cell cycle process, downregulating the Wnt signalling pathway and inducing apoptosis mainly through caspase-independent programmed cell death through mitochondrial dysfunction, activation of ER-UPR, disruption of DNA repair mechanisms and inactivation of the cell cycle process through the downregul ation of main genes in proliferation such asFOXM1 and its downstream genes. The combined treatment exerted its cytotoxic effect through upregulation of genes in stress response activation and cytostatic effects demonstrated by downregulation of main regulator genes in the cell cycle. Selected genes involved in particular pathways includingATF6,DDIT3,GADD34,FOXM1,CDK1 andp21 displayed concordant patterns of gene expression between RNA sequencing ...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research