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

TL;DR

HS1002 is a new peptide that fights prostate cancer by targeting two key proteins, reducing cancer growth and boosting the immune response.

Contribution

HS1002 is a novel peptide that dual targets GnRHR and hTERT to enhance antitumor activity in prostate cancer.

Findings

HS1002 showed highest cytotoxicity against LNCaP prostate cancer cells.

HS1002 suppressed hTERT expression and telomerase activity, reducing metastasis and promoting apoptosis.

HS1002 enhanced anticancer immunity by increasing granzyme B and IFN-γ in CD8+ T 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.

HS1002, a new peptide targeting GnRHR and hTERT, demonstrates significant Anticancer activity in prostate cancer cells. The mechanism of HS1002 can be attributed to the reduction of serum testosterone levels by desensitization of GnRHR, the downregulation of hTERT expression and telomerase activity, and the enhancement of Anticancer immunity. These findings suggest HS1002's potential as a novel therapeutic agent against prostate cancer.

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