Faculty Collaboration Database

Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions. Cancer Res 2008 Jun 15;68(12):4945-57

Date

06/19/2008

Pubmed ID

18559542

Pubmed Central ID

PMC2892791

DOI

10.1158/0008-5472.CAN-08-0568

Scopus ID

2-s2.0-49649121330 (requires institutional sign-in at Scopus site)   111 Citations

Abstract

Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.

Author List

Mallery SR, Zwick JC, Pei P, Tong M, Larsen PE, Shumway BS, Lu B, Fields HW, Mumper RJ, Stoner GD

MESH terms used to index this publication - Major topics in bold

Administration, Topical
Adult
Aged
Blotting, Western
Carcinoma in Situ
Carcinoma, Squamous Cell
Cyclooxygenase 2
Female
Fruit
Gels
Humans
Male
Middle Aged
Mouth Neoplasms
Neoplasm Invasiveness
Nitric Oxide Synthase Type II
Phytotherapy
Precancerous Conditions