Investigation of anticancer effects of 1,8-cineole in P53 mutant colon cancer cells

Colon cancer (CC) is one of the most common cancers worldwide and poses a significant health problem for both men and women. Despite advances in early diagnosis and treatment, treatment of advanced-stage colon cancer remains challenging. Chief among these challenges is the drug resistance that cancer cells develop to chemotherapy and other treatment modalities. P53 mutations observed in colon cancer cells mediate the development of cellular drug resistance, leading to cancer cells evading apoptosis and increasing their ability to metastasize. In addition to combined treatment options, the use of natural compounds to enhance the effectiveness of cancer drugs and reduce drug resistance is an increasingly popular approach to overcoming these challenges. 1,8-cineole is a monoterpene essential oil component found in various plants. This compound is reported to exhibit anti-inflammatory, antioxidant, and anticancer properties. Additionally, studies have shown that 1,8-cineole may enhance chemotherapeutic efficacy by reducing drug resistance in cancer cells. In this study, we aimed to investigate the effects of 1,8-cineole on cytotoxic, genotoxic, and drug resistance genes against colon cancer cells with P53 mutations. Cell viability was determined using MTT assays after separate and combined applications of the standard chemotherapeutic drug 5-Fluorouracil (5-FU) and 1,8-cineole on HT-29 human colon cancer cells. The effects of the compounds on DNA damage were then analyzed using single-cell gel electrophoresis. The study also investigated the effects of 1,8-cineole on mRNA expression levels of ABCB1, ABCG2, and ABCC2 genes, which contribute to drug resistance in cancer cells. The results were analyzed using appropriate statistical methods. Our results showed that 1,8-cineole, both alone and in combination with 5-FU, significantly reduced HT-29 colon cancer cell viability (p<0.05). DNA damage levels were slightly increased in the 5-FU-treated groups (p<0.05). However, no genotoxic effects were observed in the cells following 1.8-cineole application. Application of 1.8-cineole with 5-FU resulted in a decrease in ABCC2 gene expression compared to the group treated with 5-FU alone. The results indicate that 1.8-cineole may have a synergistic effect with 5-FU.