Investigation of the effects of Theranekron and Sorafenib treatments on carcinogenesis, apoptosis and biochemical profile in hepatocellular carcinoma in rats

Abstract

This study aimed to investigate the effects of Tarantula cubensis alcohol extract (TCAE, Theranekron) and Sorafenib (S) treatments on carcinogenesis, apoptosis and biochemical profile of rats with experimentally induced hepatocellular carcinoma (HCC). In the presented study, 58 male rats were divided into 7 groups; Negative Control (NC, n = 6), NC + TCAE (NCT, n = 6), NC + Sorafenib (NCS, n = 6), Positive Control (PC, n = 10), Positive Control + TCAE (PCT, n = 10), Positive Control + Sorafenib (PCS, n = 10), Positive Control + TCAE + Sorafenib (PCTS, n = 10). The active ingredients Diethylnitrosamine (DEN, 120 mg/kg, single dose) and Nitrosomorpholine (NMOR, 50 ppm, 21 weeks orally) were used to induce HCC in rats. At the end of the experiment, the animals were euthanized under appropriate conditions and samples were collected for biochemical and pathological investigations. In the PC group, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) levels were higher (p < 0.001) and urea levels were lower (p < 0.001) compared to all other groups. Treatment groups reorganized the relevant markers (ALT, AST, GGT, and urea). A significant increase was detected in Caspase-10, Caspase-3 and Granzyme-B (GrzB) (p < 0.001) in blood and Caspase-10 and GrzB (p < 0.05) in liver tissue in PCT, PCS and PCTS groups compared to the PC group. Histopathological examination revealed that the PC group showed cancer morphology, and the treatment groups caused a decrease in tumor incidence and size. Our current findings suggest that the mechanism of action of TCAE in HCC is through the NKs/CTLs-GrzB-Casp10-Casp3 signaling pathway and can be used in combination with chemotherapy drugs for the development of future drug designs.

Keywords:

• Caspase-3
• caspase-10
• Granzyme-B
• hepatocellular carcinoma
• Sorafenib
• Theranekron

Author contributions

Dr. Kurtoglu and Dr. Vanli designed the study. Experimental and biochemical procedures were performed by Dr. Vanli and Dr. Alan. Dr. Akcakavak and Dr. Ozdemir performed all pathological procedures. All authors read and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data used to support the findings of this study are available from the corresponding authors on request.

Additional information

Funding

Blood plasma and liver tissue samples obtained from the study supported by the Selcuk University Animal Experiments Ethics Committee Decision dated 25.09.2020 and numbered 2020/33 and the BAP project numbered 20212025 were used.