title: Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.
abstract: BACKGROUND
  Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL).
  
  
  METHODS
  Precancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots.
  
  
  RESULTS
  Fluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (p<0.001). Pretreatment of SCC cells with 10(-8) or 10(-7)M CAL could result in a significant cell death (p<0.05) and an elevation of CPOX protein level.
  
  
  CONCLUSIONS
  Topical CAL can improve the efficacy of ALA-PDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production.
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yang
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC.
authors.forename: Jia-Haur
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan, ROC; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
authors.affiliation: University of Colorado Denver Cancer Center, CO, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Life Science, Tzu Chi University, Hualien, Taiwan, ROC.
authors.forename: Jeng-Woei
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital, Taipei, Taiwan; Institute of Biomedical Sciences, Mackay Medical College, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC; Department of Pathology and Laboratory Medicine, Taoyuan Armed Force General Hospital, Taiwan.
authors.forename: Junn-Liang
authors.initials: JL
authors.lastname: Chang
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC; Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC; Institute of Biomedical Technology, Chung Yuan Christian University, Taoyuan, Taiwan, ROC. Electronic address: ivyhsu@cycu.edu.tw.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D002610:Cheek; D006224:Cricetinae; D003879:Dermatologic Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003879:Dermatologic Agents; D017319:Photosensitizing Agents; C055085:calcipotriene; D000622:Aminolevulinic Acid; D002117:Calcitriol
keywords: 5-Aminolevulinic acid; Calcipotriol; Hamster buccal pouch precancer; Oral precancerous lesions; Topical photodynamic therapy