2. Academic Validation
  3. Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway

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

  • J Ethnopharmacol. 2016 Dec 24:194:549-558. doi: 10.1016/j.jep.2016.10.030.
Peter M Waziri 1,  Rasedee Abdullah 2,  Swee Keong Yeap 3,  Abdul Rahman Omar 4,  Ahmad Bustamam Abdul 5,  Nur Kartinee Kassim 6,  Ibrahim Malami 7,  Thiruventhan Karunakaran 8,  Mustapha Umar Imam 9
Affiliations

Affiliations

  • 1 MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia; Department of Biochemistry, Kaduna State University, Main Campus, PMB 2336 Kaduna, Nigeria. Electronic address: [email protected].
  • 2 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 3 Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 4 Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 5 MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 6 Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 7 MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 8 Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia. Electronic address: [email protected].
  • 9 School of Public Health, Zhengzhou University, Zhengzhou City, Henan Province, PR China. Electronic address: [email protected].
PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030
Abstract

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.

Keywords

Apoptosis; Bax; Bcl 2; Clausenidin; Liver cancer; MMP.

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