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

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.

• Authors: Peter M Waziri, Rasedee Abdullah, Rosita Rosli, Abdul Rahman Omar, Ahmad Bustamam Abdul, Nur Kartinee Kassim, Ibrahim Malami, Imaobong C Etti, Ja’afaru M Sani, Mohd Azmi Mohd Lila, Jesse Faez Firdaus Abdullah
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 19 Issue 4 Pg. 917-922 (Apr 25 2018) ISSN: 2476-762X [Electronic] Thailand
• PMID: 29693341 (Publication Type: Journal Article)
• Copyright: Creative Commons Attribution License

Chemical References

• Carbazoles
• Plant Extracts
• Reactive Oxygen Species
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• clausenine
• Caspase 3

Topics

• Apoptosis (drug effects)
• Carbazoles (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Caspase 3 (metabolism)
• Cell Proliferation (drug effects)
• Clausena (chemistry)
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Plant Extracts (pharmacology)
• Reactive Oxygen Species (metabolism)
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A (metabolism)