title: Clausenidin induces caspase-dependent apoptosis in colon cancer.
abstract: BACKGROUND
  Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.
  
  
  METHODS
  We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.
  
  
  RESULTS
  Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p < 0.05) dose-dependent increase in apoptotic cell population. The DNA fragmentation assay also showed apoptotic features in the clausenidin-treated HT-29 cells. Clausenidin treatment had caused significant (p < 0.05) increases in the expression of caspase 9 protein and gene in HT-29 cells and mitochondrial ROS and mitochondrial membrane depolarization. The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells.
  
  
  CONCLUSIONS
  Clausenidin induces a caspase-dependent apoptosis in colon cancers through the stimulation of the mitochondria. The study demonstrates the potential of clausenidin for use in the treatment of colon cancers.
authors.affiliation: MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia. petermwaziri@gmail.com.|Department of Biochemistry, Kaduna State University, Main Campus, PMB 2336, Kaduna, Nigeria. petermwaziri@gmail.com.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Waziri
authors.affiliation: Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Rasedee
authors.initials: R
authors.lastname: Abdullah
authors.affiliation: Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
authors.affiliation: Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Nur Kartinee
authors.initials: NK
authors.lastname: Kassim
authors.affiliation: MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Malami
authors.affiliation: Laboratory of Vaccine and Therapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Chee Wun
authors.initials: CW
authors.lastname: How
authors.affiliation: MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Imaobong Christopher
authors.initials: IC
authors.lastname: Etti
authors.affiliation: Enzyme Technology Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Mary Ladidi
authors.initials: ML
authors.lastname: Abu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054700:Clausena / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D039681:Pyranocoumarins / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D039681:Pyranocoumarins; D017382:Reactive Oxygen Species; D020169:Caspases
keywords: Apoptosis; Caspase 9; Clausenidin; Colon cancer; MMP; bax; bcl 2