Epigallocatechin-3-gallate effectively attenuates skeletal muscle atrophy caused by cancer cachexia.

摘要

Cachexia, also known as wasting syndrome notably with skeletal muscle atrophy, costs nearly one-third of all cancer deaths in man. (-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenolic component in green tea, is a potent preventive against cachexia as well as cancers. However, how EGCG counteracts cachexia-provoked muscle wasting is unclear. EGCG was demonstrated to be able to retard tumor progression as well as to prevent body weight from loss, because EGCG attenuates skeletal muscle leukocytic infiltration and down-regulates tumor-induced NF-kappaB and E3-ligases in muscle. In mice, the dosages optimized against cachexia were determined to be 0.2 mg/mouse/day for prevention and to be 0.6 mg/mouse/day for treatment. Anti-cachexia effects were assessed using the LLC tumor model. Mice with the same body weight were divided into groups, including control, tumor bearing, and tumor-bearing but receiving water or EGCG in both prevention and treatment experiments. RT-PCR was used to assess mRNA expressions of NF-kappaB, MuRF 1, and MAFbx. The intracellular NF-kappaB, MuRF 1 and MAFbx were determined and quantified by immunofluorescence and Western blotting, respectively. Our results conclude EGCG regulates the expressions of NF-kappaB as well as downstream mediators, MuRF 1 and MAFbx, so EGCG may be an appropriate agent to be included in ensemble therapeutics of the tumor-induced muscle atrophy.