Determination of cytotoxic and apoptotic effects of essential oil of Ziziphora clinopodioides Lam. subsp. rigida (Boiss.) Rech.f. (Lamiaceae)

Plants have been used throughout human history to treat various diseases, including cancer. Nowadays, many studies are being carried out to reveal the secondary metabolites of plants and their mechanisms of action. Research on agents that do not harm healthy tissues and have anti-carcinogenic effects has become very popular in recent years. Extracts and essential oils obtained from plants also provide a wide source of potential drugs, considering their chemical content. The aim of this study was to obtain essential oil from the Ziziphora clinopodioides subsp. rigida, which was widespread in Iran and frequently consumed by humans, to analyze the chemical content of the essential oil, and to examine the effects of essential oil on cytotoxicity activities and apoptosis on colorectal cancer cell lines (CACO-2 and HCT116). The healthy embryonic cell line HEK293 was used as a control. Apoptosis analyzes were performed by Annexin FITC/PI staining using the EC50 values. mRNA was isolated to measure the levels of apoptosis-related genes (Bax, Bcl2, Caspas 3, Caspas 8 and Caspas 9) and all measurements were carried out by qRT-PCR. According to the results, it was shown that the cytotoxicity effect of Z. clinopodioides subsp. rigida essential oil on colorectal cancer cell lines was higher than its effect on healthy cell lines. As a result of the apoptosis analysis, it was shown that Z. clinopodioides subsp. rigida essential oil has a high apoptosis effect and also inhibits the antiapoptotic gene (BCL2) and induces apoptosis by promoting apoptotic genes (BAX, Caspase 3, Caspase 8 and Caspase 9). In conclusion, the results of the study conducted have shown for the first time that the Z. clinopodioides subsp. rigida has the potential to be a therapeutic agent against colorectal cancer.