Delta-Tocotrienol: Radiation Protection and Effects on Signal Transduction Pathways

摘要

Summary and Conclusions: Survival of gamma-irradiated mouse bone marrow and primary human hematopoietic CD34+ cells was significantly enhanced by Delta-tocotrienol (DT3). DT3 dramatically induced Erk phosphorylation and decreased the DNA-damage marker gamma-H2AX foci formation. DT3 reversed the radiation-inhibited mTOR and S6 protein activation, and induced 4EBP-1 phosphorylation. Knockdown of Erk gene expression by siRNA abrogated DT3- induced mTOR phosphorylation, induced gamma-H2AX foci formation, and inhibited clonogenicity in CD34+ cells. In conclusion, our data suggest DT3 effectively protects mouse bone marrow and human CD34+ cells from radiation damage through the Erk/mTOR survival pathway (Hematological 2010; 95(12) 1996-2004).