Combination of Zerumbone with 5-FU for More Effective Colorectal Cancer Treatment

Combination of Zerumbone with 5-FU for More Effective Colorectal Cancer Treatment
Miss Razieh Dehghan,¹ Dr Rezvan Najafi,² Dr Massoud Saidijam,³ Dr Razieh Amini,^4,*
1. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
4. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Introduction: Colorectal cancer is the third most common cause of cancer-related mortality in the world. Despite conventional therapies, survival time in the advanced stages of the disease is still very low. Chemotherapy resistance is one of the leading causes of death in patients with colorectal cancer. Chemotherapy based on 5-fluorouracil is the only first-line drug for the treatment of colorectal cancer that causes therapeutic limitations due to drug resistance. Chemical resistance is mainly associated with the change in the status of cancer cells from epithelial to mesenchymal (EMT). Overcoming resistance to treatment is one of the most important challenges in the treatment of cancer patients. Herbal remedies, including herbal derivatives, are widely used to treat various cancers. Zerumbone is a promising herbal compound that is widely used to treat a variety of tumors. The use of herbal supplements that do not have specific side effects can be effective in increasing the response to treatment and overcoming resistance to chemotherapy through the synergistic effect of chemical drugs and by targeting similar mechanisms. Therefore, the aim of this study was to investigate the effect of Zerumbone on the sensitization of cancer cells in response to 5-FU drug and the use of this compound in combined cancer treatment regimens.
Methods: The cytotoxic effects of ZER and 5-FU alone or 5-FU combined with ZER on the SW48 and HCT-116 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The mRNA and protein level of β-catenin, Survivin and Vimentin were measured in 5-FU, ZER, 5-FU+Zerumbone treated CRC cells using RT-qPCR and western blot.
Results: Our results demonstrated that proliferation of HCT-116 and SW48 cells that were treated with ZER ,5-FU and 5-FU+ZER was significantly reduced compared to controls. Furthermore the Gene and protein expression level of Survivin, Vimentin and β-catenin in our treatment groups were significantly reduced compared to control groups. ZER and 5-FU treatment sometimes have a strengthening effect on each other and in some cases reinforced each other's unresponsiveness. Therefore ZER treatment could increase 5-FU sensitivity in CRC chemoresistance cells, which is represented that the therapeutic potential of ZER alone and together with 5-FU could be a promising therapeutic strategy in overcoming chemoresistance, a strategy that may ultimately be applicable to other human tumors in future as well.
Conclusion: Regarding to the importance of cancer chemotherapy resistance which reduces patient response and consequently increases the risk of progression, the herbal supplements with minimum side effects can be effective in enhancing the response to treatment. Synergistic and potentiating effect of combination therapy using herbal and chemical drugs can improve patient response. Therefore, here we aimed to investigate the effect of ZER on the sensitization of cancer cells to 5-FU by evaluation of expression of main genes involved in major cellular processes.
Keywords: Colorectal cancer (CRC), Zerumbone (ZER), 5-Fluorouracil (5-FU), Chemotherapy