Synergic effects of DL-limonene, R-limonene, and cisplatin on AKT, PI3K, and mTOR gene expression in MDA-MB-231 and 5637 cell lines

The anticancer and cytotoxic effects of DL-Limonene and R-Limonene are well-documented. However, the role of natural compounds in enhancing the efficacy of platinum-based drugs like Cisplatin (CisPt) remains debated. This study aims to boost Cisplatin's impact on breast (MDA-MB-231) and bladder (5637) cancer cells using DL-Limonene and R-Limonene. Different concentrations of DL-Limonene, R-Limonene, and Cisplatin, combined, were used to treat MDA-MB-231 and 5637 cells in this experimental study. The cell's viability was evaluated using an MTT assay. AnnexinV- PI staining was applied to evaluate the percentage of apoptotic cells. Cytotoxicity results showed that combining DL-Limonene, R-Limonene, and Cisplatin significantly improved outcomes in MDA-MB-231 cells (P < 0.05). Annexin/PI staining revealed apoptosis rates of 74 %, 28 %, 43 %, 81 %, and 91 % for Cisplatin40, R-Limonen1000, DL-Limonen1000, R-Limonen1000/DL-Limonen1000, and the combined treatment, respectively, versus 13 % in the control. The combination also resulted in the greatest reduction of AKT, PI3K, and mTOR gene expression. Our results show that R-Limonene and DL-Limonene enhance Cisplatin's cancer-inhibiting effects in breast and bladder cancer cell lines. These compounds may be promising for combination therapy, potentially allowing for lower doses of chemotherapy and reducing side effects like nephrotoxicity.