Amirah Abdul Rahman, Suzana Makpol, Rahman Jamal, Roslan Harun, Norfilza Mokhtar and Wan Zurinah Wan Ngah
Posters-Accepted Abstracts: Biol Syst Open Access
The concept of multi-target therapeutic is to obtain highly effective and safe therapy with low side effects. Epigallocatechingallate (EGCG) displays many therapeutic effects, including antioxidant, anti-inflammatory, anticancer and immunomodulatory effects. Meanwhile, hydroxychavicol (HC) selectively kills cancer cells via ROS generation without affecting normal cells. Combining these bioactives yield synergistic interaction. Thus, this study focuses on unraveling the molecular mechanism that contributes to the synergistic effects of bioactive mixtures using the â�?�?omicsâ�? technology. High-throughput RNA sequencing (RNA-seq) was performed to explore the transcriptomic changes of human glioma 1321N1 and LN18 cell lines treated with combined EGCG+HC bioactives. Approximately 30-50 million high-quality reads were generated for each sample. A total of 2103 and 2442 genes were differentially expressed in 1321N1 and LN18 cells respectively (FDR P<0.05, fold-change>1.5), when treated with combined EGCG+HC, where 1025 genes were found to be commonly expressed in all treatments. Only 26 genes were commonly expressed in both cell lines treated with EGCG alone, whereas 268 genes were commonly expressed in both cell lines treated with HC alone. The genes induced by EGCG+HC treatment were grouped into functional networks such as apoptosis, cell cycle regulations, axon guidance, cytoskeleton organization, response to endoplasmic reticulum stress, inflammatory response, DNA repair, and telomere maintenance by bioinformatics analysis. Furthermore, subnetwork analysis of differentially expressed genes in 1321N1 and LN18 cells revealed five similar central genes, AKT1, ATF4, EIF2AK3, HIF1A, and NFE2L2. Taken together, the data provide evidence that the synergistic anticancer effect of EGCG+HC are influenced by both common and unique genes and pathways, that perhaps depend on the mutational status of each cell lines tested. Furthermore, combined EGCG+HC treatment was shown to enhance the effects of each individual bioactive by increasing the expression of genes present in EGCG or HC treatment alone, and/or by inducing the expression of other genes.