Areca nut extract treatment down-regulates involucrin in normal human oral keratinocyte through P13K/AKT activation.
Areca (betel) is an important etiological factor linked to the high prevalence of oral carcinoma and other oral diseases in South Asians. Involucrin is a key component of the cornified envelop and a differentiation marker of keratinocyte. In this study, we found that 5 microg/ml non-toxic areca nut extract (ANE) treatment resulted in the 0.5-fold down-regulation of involucrin and disruption in involucrin distribution in normal human oral keratinocyte (NHOK). Progressive down-regulation of involucrin during oral carcinogenesis was noted. Activation of AKT by 1.7-fold and up-regulation of COX-2 by 2-fold were elicited following ANE treatment in NHOK. Treatment with PI3K/AKT blockers reverted the down-regulation of involucrin. ANE also down-regulated involucrin by 0.6-fold and disturbed both cornified envelope and cell aggregation in calcium-induced differentiated NHOK. However, such phenomena seemed to be independent from the ANE-associated COX-2 activation. The ANE-associated down-regulation of involucrin through AKT pathway could underlie the areca-associated epithelial pathogenesis.
Tseng
Yu-Hsin
YH
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Chang
Che-Shoa
CS
Liu
Tsung-Yun
TY
Kao
Shou-Yen
SY
Chang
Kuo-Wei
KW
Lin
Shu-Chun
SC
D000328:Adult; D000368:Aged; D001114:Areca / Q000737:chemistry; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010936:Plant Extracts; D011498:Protein Precursors; D012333:RNA, Messenger; C032253:involucrin; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt