Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells

Background Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells. Methods and results Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and gamma-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC-MS/MS and GC-MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 mu g/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 mu g/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.). Conclusion As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer. [GRAPHICS] .

Automated summary

This study aims to investigate the metabolite profile and the mechanism of anticancer effect of Cedrus libani tar on colon cancer cells. The results show that Cedrus libani tar has a high cytotoxic effect on colon cancer cells and increases ROS production. Metabolite analysis reveals the presence of abundant fatty acids, phenolic compounds, and organic acids in Cedrus libani tar.