title: Kelussia odoratissimaMozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo.
abstract: BACKGROUND
  The aim of this study was to evaluate the anticancer potential ofKelussia odoratissima. Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action.
  
  
  METHODS
  K. odoratissimamethanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated.
  
  
  RESULTS
  Our results demonstrated thatK. odoratissimahas an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2.
  
  
  CONCLUSIONS
  This study demonstrated thatK. odoratissimaexhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.affiliation: School of Medicine, Taylor's University, Subang Jaya.
authors.forename: Aditya
authors.initials: A
authors.lastname: Arya
authors.affiliation: Centre for Natural Products Research and Drug Discovery.
authors.forename: Mehran
authors.initials: M
authors.lastname: Fadaeinasab
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Razavi
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajrezaei
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Ataul
authors.initials: A
authors.lastname: Karim Khan
authors.affiliation: Centre for Natural Products Research and Drug Discovery.
authors.forename: Hapipah
authors.initials: H
authors.lastname: Mohd Ali
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur; Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Pulau Pinang, Malaysia.
authors.forename: Mohamad Ibrahim
authors.initials: MI
authors.lastname: Noordin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008968:Molecular Conformation; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Kelussia odoratissima; MCF7; apoptosis; breast cancer; chemoprevention; intrinsic pathway