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Abstract
Tacrolimus (TAC) and Sirolimus (SRL) are produced by Streptomyces sp and effective immunosuppressive drugs commonly used in organ transplantation. Therefore, strategies for minimizing the toxicity of immunosuppressant molecules are our interest. This study was conducted to evaluate the interactive effects and the possible underlying mechanism of TAC and SRL on HCT116 cells. It was found that TAC and SRL alone inhibited cell viability. Also, it induced reactive oxygen species (ROS) formation, loss of mitochondrial membrane potential (Δψm), and able to increase DNA fragmentation in a concentration-dependent manner. The use of combined SRL and TAC showed a reservation in all toxicity observed with the two immunosuppressive drugs separately. Our result demonstrated that the mechanisms of TAC and SRL at high concentration are closely connected with oxidative stress. Furthermore, SRL at low concentration plays a protective effect against TAC (IC50) which induced cytotoxicity and genotoxicity. However, using the combination of the SRL/TAC at high concentrations (IC30) appears as an antagonist response.