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February 17, 2026MedComm0 citationsOpen Access

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

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SLSu Hyun LeeJLJoo Chan LeeSSSwati Sharma

Key Points

  • This research investigates the anticancer effects of HS1002 on prostate cancer cells by targeting hTERT and GnRHR.
  • HS1002 was synthesized based on GnRH and hTERT sequences.
  • Cytotoxicity of HS1002 was tested on various prostate cancer cell lines, focusing on LNCaP cells.
  • Molecular docking interactions between HS1002 and GnRHR were analyzed.
  • Inhibition of hTERT expression and telomerase activity was measured in xenograft models.
  • Effects on T cell immunity were evaluated in MC38 syngeneic mice.
  • HS1002 showed increased cytosolic calcium influx in HEK293 cells expressing GnRHR.
  • LNCaP cells exhibited the highest sensitivity to HS1002, with significant cytotoxic effects.
  • HS1002 decreased hTERT expression, leading to reduced metastasis and enhanced apoptosis and autophagy.
  • The peptide inhibited tumor growth in xenograft models and downregulated hTERT expression in tumor tissues.
  • HS1002 increased granzyme B and IFN‐γ production in CD8 + T cells.

Abstract

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.

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Cite This Study

Lee et al. (2026) studied this question.

synapsesocial.com/papers/6994058c4e9c9e835dfd6766https://doi.org/10.1002/mco2.70630
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