Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1α-VEGF signaling axis

Abstract

A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Previously, we have shown that GV1001 interacts with heat shock proteins (HSPs) and penetrates cell membranes to be localized in the cytoplasm. In this study, we have found that GV1001 lowered the level of intracellular and surface HSPs of various cancer cells. In hypoxic conditions, GV1001 treatment of cancer cells resulted in decreases of HSP90, HSP70, and HIF-1 alpha. Subsequently, proliferation of cancer cells and synthesis of VEGF were significantly reduced by treatment using GV1001 in hypoxic conditions. In an experiment using a nude mouse xenograft model, GV1001 exerted a similar tumor suppressive effect, further confirming its anti-tumor efficacy. Higher apoptotic cell death, reduced proliferation of cells, and fewer blood vessels were observed in GV1001-treated tumors compared to control. In addition, significant reduction of Tie2+ CD11b+ monocytes, which were recruited by VEGF from tumor cells and play a critical role in angiogenesis, was observed in GV1001-treated tumors. Collectively, the results suggest that GV1001 possesses potential therapeutic efficacy in addition to its ability to induce anti-cancer immune responses by suppressing both HSP70 and HSP90. (C) 2013 Elsevier Ltd. All rights reserved.