Clausenidin from Clausena excavata Burm. causes Apoptosis of Liver Cancer in Mice

Document Type : Research Articles

Authors

1 Department of Biochemistry, Kaduna State University, Kaduna, Nigeria.

2 Department of Medical Biochemistry, Usmanu Danfodio University, Sokoto, Nigeria.

3 Centre for Advanced Medical Research and Training, Usmanu Danfodio University, Sokoto, Nigeria.

4 Department of Pharmacology, Kaduna State University, Kaduna, Nigeria.

5 Department of Chemistry, Kaduna State University, Kaduna, Nigeria.

6 Department of Anatomic Pathology and Forensic Medicine, Kaduna State University, Kaduna, Nigeria.

7 Department of Medical Microbiology and Parasitology, Kaduna State University, Kaduna, Nigeria.

Abstract

Background: Clausenidin is a pyranocoumarin that was isolated from the roots of Clausena excavata Burm. Previously, the pure clausenidin crystals were successfully used to treat HepG2 cells (liver cancer) in vitro; however, no in vivo study had been conducted to support these findings. Therefore, the current study was designed to investigate the in vivo anti-liver cancer effect of pure clausenidin in hepatocellular carcinoma-induced BALB/c mice. Method: DNA fragmentation, caspases, and histological assays were conducted to evaluate the cytotoxic effect of the pure clausenidin, while real-time qPCR was performed to monitor the expression of apoptosis-inducing genes in the clausenidin-treated mice. Result: Clausenidin significantly (p<0.05) decreased the liver damage-induced levels of alanine and aspartate aminotransferases and also caused fragmentation of the genomic DNA of the tumors. This was followed by a significant increase (p<0.05) in the expression of caspases 3, 8 and 9 proteins in the clausenidin-treated mice. In addition, clausenidin upregulated the expression of  pro-apoptotic genes associated with the extrinsic and intrinsic pathways. However, it was observed that clausenidin may have inhibited angiogenesis by downregulating the expression of the VEGF gene in the treated mice. Conclusion: Therefore, clausenidin can be potentially used as an anti-liver cancer agent.  

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