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Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway


Waziri, Peter M. and Abdullah, Rasedee and Swee, Keong Yeap and Omar, Abdul Rahman and Abdul, Ahmad Bustamam and Kassim, Nur Kartinee and Malami, Ibrahim and Karunakaran, Thiruventhan and Imam, Mustapha Umar (2016) Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway. Journal of Ethnopharmacology, 194 (2016). pp. 549-558. ISSN 0378-8741; ESSN: 1872-7573


Ethnopharmacological relevance: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia. Aim of the study: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis. Materials and methods: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using 1H and 13C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays. Results: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells. Conclusion: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Science
Faculty of Veterinary Medicine
Institute of Bioscience
DOI Number: https://doi.org/10.1016/j.jep.2016.10.030
Publisher: Elsevier
Keywords: Clausenidin; Apoptosis; Liver cancer; MMP; Bcl 2; Bax
Depositing User: Mohd Hafiz Che Mahasan
Date Deposited: 07 Nov 2017 02:47
Last Modified: 07 Nov 2017 02:47
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.jep.2016.10.030
URI: http://psasir.upm.edu.my/id/eprint/55287
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