The roles of kaempferol on anti-tumor effects of doxorubicin

Liver cancer or hepatocellular carcinoma (HCC) is primary tumor seen with chronic liver disease in general. The fifth common type of cancer in the world and the third major cause of cancer-related deaths worldwide. Nowadays, there are new developments in treatment of chronic didease and anthracyclines has an important place in the treatment of cancer. Anthracyclines seems to be any alternative in the treatment of many tumors, such as hepatocellular carcinoma and efforts to reduce its side effects are also very important. In this study, we investigated that a flavonoid Kaempferol (Kaem)'s role enhancing anti-tumor effect and educing the side effects of Doxorubicin (Dox) on Hep-G2 cell lines. The cytotoxic effect of independent and combined of Dox and Kaemferol was determined by MTT assay and also some biological activities were measured with some methods, morphological effects of apoptosis by AO/EB double staining, apoptotoic membran by Annexin V-FITC flowcytometer method, cell cycle analysis by flow cytometric analysis, Caspase 3 and -9 activities by colorimetrically. In results, Hep-G2 cell viability was decreased dose and time-dependent. IC50 values were determined in 48 hours, 0,5 and 100µM for Kaem and Dox, respectively. After exposure of the test compounds, Dox, Kaem and combinations were caused to increase apoptotic index significantly. In cell cycle analysis, When Dox and Kaempferol applied independently, G2-arrested cell ratio is relatively low. In conrast, when applied in combination, the ratio of G2-arrested cells were found to be very high. According to results of Annexin V-FITC flowcytometer analysis, the number of early apoptotic cells have attracted attention in combination treatment (1µM Dox+150 µM). In anaother analysis, It was determined that all of the combination doses increased the caspase 3 enzyme activity. Finnaly, we commented Kaempferol preserved cells against Doksorobisin-dependent side effects also increase anti-tumor effect. Kaempferol is a potential drug both combination and indipendently for the effective treatment of HCC. Keywords:Hepatocellular carcinoma, Doxorubicin, Kaempferol, cytotoxicity, apoptosis.