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Updated: Jul 19, 2026

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
Areca nut extract treatment down-regulates involucrin in normal human oral keratinocyte through P13K/AKT activation
Yu-Hsin Tseng1, Che-Shoa Chang, Tsung-Yun Liu
1Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Abstract:
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.
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