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Effect of Epigallocatechin-3-Gallate on Hypoxia-Inducible Factor-1 Synthesis

Sze-Kwan Lin, BDS, MS, PhD; Chia-Tung Shun, MD; Sang-Heng Kok, BDS; Chih-Chiang Wang, MS; Tzu-Yu Hsiao, PhD; Chia-Ming Liu, MD

Arch Otolaryngol Head Neck Surg. 2008;134(5):522-527.

Objective  To verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on the synthesis of hypoxia-induced vascular endothelial growth factor (VEGF) in nasal polyp fibroblasts (NPFs).

Design  Eight primary cultures of NPFs were established from nasal polyps. Effects of EGCG on the production of hypoxia-inducible factor (HIF)–1 (the most potent VEGF stimulant) and VEGF by NPFs under hypoxic conditions were measured by Western blot analysis. Immunohistochemical staining was used to examine the in vivo expressions of HIF-1 and VEGF in 20 sections of nasal polyps.

Results  Western blot analysis showed that cobalt chloride induced HIF-1 and VEGF synthesis in NPFs in a time-dependent manner, reaching a plateau at 4 and 8 hours, respectively, following treatment. Epigallocatechin-3-gallate attenuated the level of HIF-1 induced by cobalt chloride and also reduced cobalt chloride–stimulated VEGF production by suppressing HIF-1 synthesis. Furthermore, oligomycin (a specific HIF-1 inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone. Nevertheless, the synergistic effect seemed smaller than the sum of their individual actions. Immunohistochemical analysis revealed the presence of HIF-1 and VEGF in NPFs and mononuclear round cells. Intimate alignment of VEGF-positive fibroblasts and proliferating small capillaries was frequently found.

Conclusions  Nasal polyp fibroblasts contribute to the pathogenesis of nasal polyps by producing VEGF to promote angiogenesis under hypoxic conditions. Epigallocatechin-3-gallate substantially diminishes HIF-1 and VEGF synthesis in NPFs.

Author Affiliations: Departments of Dentistry (Drs Lin and Kok), Forensic Medicine (Dr Shun), and Otolaryngology (Drs Hsiao and Liu) and Graduate Institute of Clinical Medicine (Dr Wang), National Taiwan University Hospital, Taipei, Taiwan.