A Novel Peptide, HS1002, Enhances Antitumor Activity via Dual Targeting of the GnRH Receptor and Human Telomerase Reverse Transcriptase in Prostate Cancer Cells

ABSTRACT Human telomerase reverse transcriptase (hTERT) is overexpressed in most human cancers and is an important target for cancer therapy. In this study, HS1002 was synthesized based on the amino acid sequences of gonadotropin‐releasing hormone (GnRH) and hTERT. This study aimed to evaluate HS1002's anticancer activity and its effects on the gonadotropin‐releasing hormone receptor (GnRHR) and hTERT in prostate cancer cells. HS1002 increased cytosolic calcium influx in GnRHR‐overexpressing HEK293 cells and showed specific molecular docking interactions with GnRHR. Compared with prostate cancer cell lines, HS1002 exhibited the highest cytotoxicity against LNCaP cells. The hTERT expression correlated with telomerase activity was suppressed by HS1002, resulting in reduced metastasis and increased apoptosis and autophagy. Additionally, HS1002 suppressed c‐Myc and ERK protein expressions in LNCaP cells. Furthermore, HS1002 inhibited tumor growth and downregulated hTERT expression in the xenograft model tumor tissues. HS1002/IL‐2‐pretreated PBMCs also exhibited potent cytotoxicity toward LNCaP cells. In addition, HS1002 increased the production of granzyme B and IFN‐γ in CD8 + T cells in MC38 syngeneic mice. These findings demonstrate that HS1002 suppresses prostate cancer cell growth and induces anticancer immunity, suggesting its potential as a novel therapeutic agent against prostate cancer.