Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-IIstimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway

Scope: This study investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin-like growth factor (IGF)-I-stimulated and IGF-II-stimulated mitogenesis in 3T3-L1 preadipocytes. Methods and results: We found that this process was dose and time dependent, and caused by suppression of IGF-I-stimulated and IGF-II-stimulated phosphorylation of p66Shc and mitogen-activated protein kinase (MAPK) pathway proteins, including MEK1 kinase (RAF1), extracellular signal-regulated protein kinase (ERK) kinase (MEK1), and ERK 1 and ERK 2 (ERK1/2), but not phospho-Jun-N-terminal kinase, protein kinase B, p52Shc, or p46Shc. Furthermore, EGCGinhibited the IGF-I-stimulated phosphorylation of the IGF-I receptor-beta (IGF-IR β), the association of IGF-IRwith the p66Shc protein, and the IGF-II-stimulated associations of the IGF-IIreceptor with G _αi-2 and p66Shc proteins, suggesting that EGCGselectively affects particular types of Shc and MAPKfamily members. Pretreatment with antiserum against the EGCGreceptor (also known as the 67-kDa laminin receptor; 67LR), but not with an adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, prevented the inhibitory actions of EGCGon IGF-I- and IGF-II-stimulated ERK1/2 phosphorylation and subsequent preadipocyte proliferation. Conclusion: The results of this study suggest that EGCGmediates anti-IGF-I and anti-IGF-IIsignals in preadipocyte mitogenesis via the 67LR but not the AMPKpathway.