Investigation of the effects of sorafenib, sertraline and piperine applications on oxidative status in liver carcinoma cell line

In this investigation, the effects of sorafenib, which is frequently used in the treatment of liver cancer, sertraline, one of the selective serotonin reuptake inhibitors, and piperine, a phytochemical, were evaluated in terms of cytotoxicity and genotoxicity in liver cancer cell line (HepG2) and healthy cell line (HUVEC). Although the cytotoxic effect of the applied combination values was observed in both cell lines during 24- and 48-hour periods compared to the control, the survival rate in cell viability was observed to be excessive in the HUVEC cell line. However, in the HepG2 cell line, decreases in cell viability were monitored in the combination studies with sorafenib and piperine combination applications, along with high-dose sertraline. In the HepG2 cell line, the lowest DNA damage (16.67±2.52) was identified in the SOR2.5+PIP7.5 combination at 24 hours; in the HUVEC cell line, the lowest DNA damage (18.00±4.00) was identified at 24 hours. In the HepG2 cell line, the highest DNA damage (105.33±7.57) was identified in SOR2.5+PIP30 combination at 48 hours; in HUVEC cell line, the highest DNA damage (49.00±2.65) was identified in SOR10+PIP30 combination at 48 hours. The combinations applied in both cell lines led to an increase in DNA damage compared to the control group. In this context, it was found that the combination of sorafenib and piperine had a greater genotoxic effect on both cell lines. A genotoxic effect was observed in the administration groups combined with a high dose of sertraline. Total antioxidant (TAS) and total oxidant (TOS) levels were determined in the HepG2 cell line over a 24-hour period. Looking at the TAS/TOS levels, the highest TAS level compared to the control group was observed in the application group SOR2.5+PIP7.5+SER0.62 (0.5247±0.10839), while; the lowest TAS level was observed in the SOR5+PIP15 (0.1315±0.07695) application group. When the applied combinations were compared with the control group, the highest TOS level was observed in SOR10+PIP30 (71.3408±1.24018) application group, while the lowest TOS level was observed in SOR2.5+PIP30 (20.6342±3.01179) application group. The increase in the amount of free radicals may be associated with TOS level. Depending on this increase, damage to DNA may occur directly or indirectly. It is thought that our findings will provide data on drug and drug interactions used in the field of oncology and will form the basis for future studies.