Clausenidin Induces Caspase 8-Dependent Apoptosis and Suppresses Production of VEGF in Liver Cancer Cells

Document Type: Research Articles

Authors

1 MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.

2 Department of Biochemistry, Kaduna State University, Main Campus, PMB 2336, Kaduna, Nigeria.

3 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia.

4 Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia

5 Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia.

6 Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Abstract

Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
carcinoma cells.

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