title: Chemopreventive effect of Phaleria macrocarpa on colorectal cancer aberrant crypt foci in vivo.
abstract: BACKGROUND
  Natural products are important ingredients for pharmaceutical applications specifically new entities for treating cancer and other diseases. Phaleria macrocarpa is native of Indonesia and considered as a prolific source of bioactive substances useful for chemoprevention.
  
  
  OBJECTIVE
  To investigate the chemopreventive properties of Phaleria macrocarpa on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats.
  
  
  METHODS
  The biological activities of the ethanol extract of P. macrocarpa fruits were evaluated both in vitro and in vivo. First the extract was investigated for its in vitro antioxidant activity by the total phenolic content and ferric reducing antioxidant power assay. Then the chemopreventive effect of P. macrocarpa was performed on AOM-induced aberrant crypt foci as colorectal carcinoma model in rats.
  
  
  RESULTS
  the crude ethanolic extract of P. macrocarpa has high antioxidant activity and modulated the oxidative stress as proved by the up-regulation of glutathione-s-transferase and superoxide dismutase. Immunohistochemical staining of the treated sections showed overexpression of PCNA and Bax, reduced crypt sizes and numbers, indicating the characteristic feature of apoptotic cancer cells. PCNA is a landmark of cell damage and turn-over and can be associated with clinical cancer mutation. The most potent doses were 250mg/kg and 500mg/kg as compared to 35mg/kg 5-fluorouracil.
  
  
  CONCLUSIONS
  In this sense, the potential modulation of the colorectal pathophysiological pathway by P. macrocarpa natural compounds mostly flavonoids offer a great possibility for the discovery of new leads towards the colorectal cancer.
authors: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: abd_um@yahoo.com.
authors: Abdrabuh N
authors: AN
authors: Shwter
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: noraziza@um.edu.my.
authors: Nor Azizan
authors: NA
authors: Abdullah
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: alshaweshmam@um.edu.my.
authors: Mohammed A
authors: MA
authors: Alshawsh
authors: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75 123, Uppsala, Sweden. Electronic address: hesham.el-seedi@fkog.uu.su.
authors: Hesham R
authors: HR
authors: El-Seedi
authors: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: nalhenhena@yahoo.com.
authors: Nawal A
authors: NA
authors: Al-Henhena
authors: Department of Experimental Hematology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. Electronic address: shaden.khalifa.2014@gmail.com.
authors: Shaden A M
authors: SA
authors: Khalifa
authors: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: ammeen@um.edu.my.
authors: Mahmood A
authors: MA
authors: Abdulla
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001397:Azoxymethane / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D029645:Thymelaeaceae / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D051028:bcl-2-Associated X Protein; D001397:Azoxymethane
keywords: Aberrant crypt foci; Antioxidant activity; Azoxythemane; Bax; PCNA; Phaleria macrocarpa