Potential therapeutic effects of chrysin and apigenin in hepatocellular carcinoma model induced with diethylnitrosamine

ABSTRACT POTENTIAL THERAPEUTIC EFFECTS OF CHRYSIN AND APIGENIN IN HEPATOCELLULAR CARCINOMA MODEL INDUCED WITH DIETHYLNITROSAMINE Hepatocellular carcinoma (HCC) is a rapidly progressive cancer with a poor prognosis and high mortality rates. The increased mortality associated with HCC leads to the need for alternative treatments. Natural products and their structural analogs are expected to provide new avenues for therapy. In this study, in which an experimental HCC model was created, it was aimed to examine the potential therapeutic effects of the individual and combined application of natural flavonoids apigenin and chrysin. In the study, rats were divided into 5 groups (Control, DEN, DEN+Apigenin, DEN+Chrysin, DEN+Combin groups). The control group was administered 0.5 mL PBS once a week for the first 2 weeks, after a 2-week break, DMSO was administered via oral gavage 4 times a week for 4 weeks, and 0.5 mL 3 times a week for the next 8 weeks. For the cancer model groups, DEN 150 mg/kg (in PBS) intraperitoneal once a week for the first 2 weeks. Done. After a two-week recovery period, 2-AAF was administered orally at a dose of 20 mg/kg 4 times a week for 4 weeks. In the continuation of the study, by oral gavage 3 times a week for 8 weeks; 0.5 ml DMSO to the DEN group, 50 mg/kg apigenin (dissolved in DMSO) to the DEN+Apigenin group, 50 mg/kg chrysin (dissolved in DMSO) to the DEN+Chrysin group, and apigenin and chrysin to the DEN+Combin group at the same doses given together. At the end of the applications, rats were decapitated and histopathological and biochemical evaluations were made in blood and liver tissue samples. Compared with the controls, in the cancer groups treated with DEN; There was an increase in STAT-3, NF-κB, CIP2A, survivin, annexin-5, smoothened, sonic hedgehog, jagged1, and notch1 levels, and a decrease in all of these parameters in the treatment groups compared to the DEN group. At the caspase-3 level; There was a decrease in the cancer groups compared to the control group, and an increase in the treatment groups compared to the DEN group. These effects were most significant in the DEN+Apigenin group. In the histopathological evaluations, the normal histological structure was observed in the liver tissues of the control group. Rats in the DEN group had 62.5% moderate-to-severe fibrosis, varying degrees of fibrosis, inflammatory lesions, regenerative nodule formation, and 87.5% moderate-to-severe inflammation. Significant reductions in these lesions and inflammation were observed in the treatment groups. This reduction was most pronounced in the DEN+Apigenin and DEN+Combin groups. As a result; It has been confirmed by the results of a histopathological and biochemical evaluation that apigenin, chrysin, and their combined treatments have chemotherapeutic effects in HCC; and that this effect is mostly achieved with apigenin treatment. Keywords: Hepatocellular carcinoma, DEN, 2-AAF, apigenin, chrysin