title: Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion.
abstract: BACKGROUND
  Drastic increment of skin cancer incidence has driven natural product-based chemoprevention as a promising approach in anticancer drug development. Apart from its traditional usages against various ailments, Ardisia crispa (Family: Myrsinaceae) specifically its triterpene-quinone fraction (TQF) which was isolated from the root hexane extract (ACRH) was recently reported to exert antitumor promoting activity in vitro. This study aimed at determining chemopreventive effect of TQF against chemically-induced mouse skin tumorigenesis as well as elucidating its possible pathway(s).
  
  
  METHODS
  Mice (n = 10) were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μl) followed by, a week later, repeated promotion (twice weekly; 20 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μl). TQF (10, 30 and 100 mg/kg) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application. Upon termination, histopathological and biochemical analysis, as well as Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and transcription factor enzyme-linked immunosorbent assay (ELISA) assays were performed to elucidate the potential mechanism of TQF.
  
  
  RESULTS
  With comparison to the carcinogen control, results revealed that lower dose of TQF (10 mg/kg) conferred antitumor promoting effect via significant (P < 0.05) suppression against lipid peroxidation (LPO), apoptotic index (cell death) and nuclear factor-kappa B (NF-κB), along with reduction of keratinocyte proliferation; whilst its higher dose (100 mg/kg) was found to promote tumorigenesis by significantly (P < 0.05) increasing LPO and apoptotic index, in addition to aggravating keratinocyte proliferation.
  
  
  CONCLUSIONS
  This study evidenced that TQF, particularly at its lower dosage (10 mg/kg), ameliorated DMBA/TPA-induced mouse skin tumorigenesis. Though, future investigations are warranted to determine the lowest possible therapeutic dose of TQF in subsequent in vivo chemopreventive studies.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. joyce_ylt86@hotmail.com.
authors.forename: Looi Ting
authors.initials: LT
authors.lastname: Yeong
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. roslida@upm.edu.my.
authors.forename: Roslida
authors.initials: R
authors.lastname: Abdul Hamid
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. latifahsy@upm.edu.my.|Institute of Biosciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. latifahsy@upm.edu.my.
authors.forename: Latifah
authors.initials: L
authors.lastname: Saiful Yazan
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. huzwah@upm.edu.my.
authors.forename: Huzwah
authors.initials: H
authors.lastname: Khaza'ai
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. norhafizahm@upm.edu.my.
authors.forename: Norhafizah
authors.initials: N
authors.lastname: Mohtarrudin
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D031644:Ardisia; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005591:Chemical Fractionation; D018890:Chemoprevention; D003474:Curcumin / Q000008:administration & dosage; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000008:administration & dosage; D018517:Plant Roots; D011809:Quinones / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D011809:Quinones; D014315:Triterpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate