title: The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach.
abstract: BACKGROUND
  Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models.
  
  
  RESULTS
  Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels.
  
  
  CONCLUSIONS
  This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Karimian
authors.forename: Mehran
authors.initials: M
authors.lastname: Fadaeinasab
authors.forename: Soheil Zorofchian
authors.initials: SZ
authors.lastname: Moghadamtousi
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajrezaei
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahedifard
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Razavi
authors.forename: Sher Zaman
authors.initials: SZ
authors.lastname: Safi
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.forename: Shaden A M
authors.initials: SA
authors.lastname: Khalifa
authors.forename: Hesham R
authors.initials: HR
authors.lastname: El-Seedi
authors.forename: Mahmood Amin
authors.initials: MA
authors.lastname: Abdulla
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.forename: Mohamad Ibrahim
authors.initials: MI
authors.lastname: Noordin
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009368:Neoplasm Transplantation; D010936:Plant Extracts / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction; D031203:Tanacetum / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007783:Lactones; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27