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Cigarette smoke condensate induces nuclear factor kappa-b activity and proangiogenic growth factors in aerodigestive cells

✍ Scribed by Joseph Rohrer; Beverly R. K. Wuertz; Frank Ondrey

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
142 KB
Volume
120
Category
Article
ISSN
0023-852X

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✦ Synopsis

Abstract

Objectives/Hypothesis:

Aerodigestive cancer risk of both lung and head and neck cancers has been linked to the genotoxic effects of tobacco use. These effects include upregulation of nuclear factor kappa‐B (NFκB) and its downstream products associated with both lung and head and neck cancer malignant progression.

Study Design:

Bench Research.

Methods:

In the present study we examined the effects of cigarette smoke condensate on functional activation of NFκB in human papillomavirus (HPV)‐transformed oral cavity cells (HOK 16B cells) and transformed bronchial epithelium (Beas2B cells) using the head and neck squamous cancer cell line, UMSCC 38, as a comparison. Luciferase reporter gene assays with two types of transiently transfected NFκB reporter genes were employed and downstream NFκB‐dependent products, interleukin‐6, interleukin‐8, and vascular endothelial growth factor, were assayed by enzyme‐linked immunosorbent assay.

Results:

All cell lines were able to dose dependently activate NFκB reporter genes after exposure to cigarette smoke condensate (P < .05). However, the HPV premalignant, transformed cell line had a much more robust NFκB response (3.45‐fold) versus the squamous cancer cell line (1.62‐fold) and SV40 transformed Beas2B (1.83). Both NFκB reporter genes had similar response curves.

Conclusions:

This study demonstrates cigarette smoke products might be more potent promoters of an NFκB‐dependent progression from HPV+ premalignancy to cancer rather than after tumors are established. Future studies should focus on abrogating NFκB increases during malignant progression and premalignancy. This might be even more relevant in the HPV+ patient with premalignancy. Laryngoscope, 2010

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