title: Chemopreventive effect of Toona sinensis leaf extract on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch squamous cell carcinogenesis.
abstract: OBJECTIVE
  Toona sinensis leaf extract (TSL) has been shown to have anti-tumor effects on cancer cell lines. This study aimed to investigate the chemopreventive potential and the underlying mechanism of TSL during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.
  
  
  METHODS
  One hundred hamsters were divided into control (n=30), carcinogenic (n=20), preventive (n=42), and therapeutic (n=8) groups. The animals in carcinogenic and preventive groups were administered reverse osmosis water (carcinogenic group) or TSL (1g/kg bw) (preventive group) by gavage daily for 4 weeks, and their bilateral pouches were painted with a 0.5% DMBA solution for 4, 9, and 12 weeks. The animals in the therapeutic group were treated with DMBA for 12 weeks prior to TSL administration for 4 weeks. Expression levels of survivin, X chromosome-linked inhibitor of apoptosis (XIAP), proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins were analyzed by immunohistochemistry. Apoptotic activity was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, cytochrome C, and poly (ADP-ribose) polymerase (PARP).
  
  
  RESULTS
  In the preventive group, the results showed significant decreases not only in the incidences of squamous cell carcinoma (SCC) (50%) and epithelial dysplasia (62.5%) but also in the tumor number, tumor volume, tumor burden, and the severity of dysplastic lesions. The down-regulation of survivin, XIAP, PCNA, iNOS, and COX-2 proteins and the increased apoptotic activity indicated anti-proliferative and apoptosis-inducing abilities of TSL on DMBA-induced HBP carcinogenesis.
  
  
  CONCLUSIONS
  The results suggested that TSL might be a promising candidate for the prevention of oral cancer.
authors.affiliation: Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dentistry, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hseng-Kuang
authors.initials: HK
authors.lastname: Hsu
authors.affiliation: Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lin
authors.affiliation: Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: k0285@ms22.hinet.net.
authors.forename: Yuk-Kwan
authors.initials: YK
authors.lastname: Chen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001551:Benz(a)Anthracenes / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011897:Random Allocation; D000077195:Squamous Cell Carcinoma of Head and Neck; D064028:Tracheophyta / Q000737:chemistry*
chemical_list: D016588:Anticarcinogenic Agents; D001551:Benz(a)Anthracenes; D010936:Plant Extracts; C046810:7,12-dihydroxymethylbenz(a)anthracene
keywords: Chemoprevention; DMBA-carcinogenesis; Hamster; Toona sinensis