Tea polyphenol epigallocatechin 3‐gallate impedes the anti‐apoptotic effects of low‐grade repetitive stress through inhibition of Akt and NFκB survival pathways

V79 Chinese Hamster lung fibroblasts were subjected to repetitive low‐grade stress through multiple exposures to 30 μM H 2 O 2 in culture for 4 weeks. Akt/protein kinase B became phosphorylated at serine 473 and threonine 308 during this period of repetitive stress. Concurrent exposure of the cells to LY294002 (5 μM), a phosphoinositide‐3 kinase inhibitor or 4.5 μM epigallocatechin 3‐gallate (EGCG), a tea polyphenol almost completely blocked Akt activation by repetitive stress. Phosphorylation of I kappa B kinase (IKK) and transcriptional activity driven by nuclear factor kappa B (NFκB) were significantly enhanced by repetitive oxidative stress. These increases were largely abolished by simultaneous exposure to EGCG. The repetitively stressed cells demonstrated a significant resistance to apoptosis by subsequent acute stress in the form of ultraviolet radiation at 5 J/m 2 or H 2 O 2 (7.5 mM). The resistance to apoptosis conferred by repetitive stress was drastically reduced (>80%) by constant exposure to EGCG during the stress period while the presence of LY294002 or the NFκB inhibitor SN50 brought about a relatively moderate effect (about 50–65%). Our data indicate that activation of Akt and NFκB pro‐survival pathways by repetitive low‐grade stress results in a strong inhibition of the normal apoptotic response after subsequent acute stress. The tea polyphenol EGCG impedes the activation of both Akt and NFκB by repetitive stress and as a result preserves the normal apoptotic response during subsequent acute stress.