The combination of Doxorubicin and Coumarin can suppress the growth of colorectal cancer cells: In silico and In vitro study

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of deaths related to cancer around the world. Currently, the clinical treatment of CRC predominantly includes surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Doxorubicin, a mediator used for anti-metabolite and anti-cancer reasons, has exhibited encouraging outcomes in the management of CRC. Coumarin is a natural antioxidant that can help reduce speed of the CRC growth. Previous research has explored the combination of coumarin and Dox in various cancer types, although its efficacy in CRC remains unexamined. To address this gap, we looked at how two drugs, Dox and coumarin, can impact the growth and death of CRC cells when used together or separately. We also studied the role of β-catenin, Twist, Cyclin D۱, and ZEB-۱ in mediating their effects. Our study worked on C۲۶ cells in vitro. The MTT test was utilized to assess cell growth, while RT-qPCR was employed to quantify the expression of β-catenin, Twist, Cyclin D۱, and ZEB-۱. Dox and Coumarin when together and by themselves are able to stop the growth. Notably, RT-qPCR analysis revealed a decrease in the expression of Twist, Cyclin D۱, and ZEB-۱ in reaction to this combination treatment, indicating that these molecules potentially facilitate the aforementioned anti-cancer effects. The molecular docking outcomes revealed that coumarin can affect Twist, Cyclin D۱, and ZEB-۱ at the protein level. In short, our findings substantiate the synergistic effect of Dox and Coumarin in impeding the development of C۲۶, while also proposing the putative involvement of the Wnt pathway as a downstream mediator in this treatment regimen. Future research can determine if this treatment can be used for colorectal cancer and how it works in the body.

کلیدواژه ها:

Colorectal cancer ، Doxorubicin ، Coumarin ، Wnt signaling