Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin

Abstract

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. The gemini nanoparticle formulation of polyphenolic curcumin significantly inhibits the viability of cancer cells. However, the molecular mechanisms and pathways underlying its toxicity in colon cancer are unclear. Here, we aimed to uncover the possible novel targets of gemini curcumin (Gemini-Cur) on colorectal cancer and related cellular pathways. After confirming the cytotoxic effect of Gemini-Cur by MTT and apoptotic assays, RNA sequencing was employed to identify differentially expressed genes (DEGs) in HCT-116 cells. On a total of 3892 DEGs (padj < 0.01), 442 genes showed a log2 FC >|2| (including 244 upregulated and 198 downregulated). Gene ontology (GO) enrichment analysis was performed. Protein–protein interaction (PPI) and gene-pathway networks were constructed by using STRING and Cytoscape. The pathway analysis showed that Gemini-Cur predominantly modulates pathways related to the cell cycle. The gene network analysis revealed five central genes, namely GADD45G, ATF3, BUB1B, CCNA2 and CDK1. Real-time PCR and Western blotting analysis confirmed the significant modulation of these genes in Gemini-Cur-treated compared to non-treated cells. In conclusion, RNA sequencing revealed novel potential targets of curcumin on cancer cells. Further studies are required to elucidate the molecular mechanism of action of Gemini-Cur regarding the modulation of the expression of hub genes.

Cytotoxic and apoptotic potential of gemini-chrysophanol nanoparticles against human colorectal cancer HCT-116 cell lines

“…In this study, Gemini-Chr NPs were successfully produced and the results revealed cytotoxicity and cell apoptosis induction in HCT-116 cells. Previous records showed no cytotoxicity of Gemini surfactants on HCT-116 cells [ 31 ], and the results of this study showed that Gemini surfactant is a little bit toxic than Gemini-Chr NPs against MEFs cells but non significant and this is probably due to the smaller size for Gemini surfactant that can more easily enter the cells. Gemini surfactant due to its biocompatibility and biodegradability properties can be used for administrating hydrophobic drugs as a safe and cost-efficient system [ 23 ], and in comparison with monovalent surfactants offer some advantages such as low critical micellization concentration and high solubilization power [ 32 ].…”