Anti-cancer effect of GV1001 for prostate cancer: function as a ligand of GnRHR

Kim, Ji Won; Yadav, Dharmendra Kumar; Kim, Soo Jin; Lee, Moo Yeol; Park, Jung Min; Kim, Bum Seok; Kim, Mi‐Hyun; Park, Hyeung Geun; Kang, Keon Wook

doi:10.1530/erc-18-0454

Cited by 14 publications

(20 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…disulfide bond Cys32-Cys35). In other words, ASK1 is in its free form to propagate p38-mediated apoptosis 48,[51][52][53][54][55][56][57][58][59] .…”

Section: Discussionmentioning

confidence: 99%

Cold atmospheric plasma generated reactive species aided inhibitory effects on human melanoma cells: an in vitro and in silico study

Yadav

Adhikari

Kumar

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Malignant melanoma is considered to be a heterogeneous disease that arises from altered genes and transformed melanocytes. In this study, special softjet cold atmospheric plasma was used to treat three different human melanoma cells using air and N 2 gases to check the anti-melanoma activity. The physical effects by plasma revealed an increase in the temperature with the gradual reduction in pH at 60 sec, 180 sec and 300 sec air and N 2 plasma treatment. Cellular toxicity revealed a decreased in cell survival (~50% cell survival using air gas and <~60% cell survival using N 2 gas at 60 sec plasma treatment in G-361 cells). Gene analysis by q-PCR revealed that 3 min and 5 min air and N 2 plasma treatment activated apoptotic pathways by triggering apoptotic genes in all three melanoma cell lines. The apoptosis was confirmed by DAPI staining and its related pathways were further explored according to protein-protein docking, and their probable activation mechanism was revealed. The pathways highlighted that activation of apoptosis which leads to cellular cascades and hence stimulation ASK1 (docking method) revealed that softjet plasma can be an effective modality for human melanoma treatment.

show abstract

“…disulfide bond Cys32-Cys35). In other words, ASK1 is in its free form to propagate p38-mediated apoptosis 48,[51][52][53][54][55][56][57][58][59] .…”

Section: Discussionmentioning

confidence: 99%

Cold atmospheric plasma generated reactive species aided inhibitory effects on human melanoma cells: an in vitro and in silico study

Yadav

Adhikari

Kumar

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to our data demonstrating effects on the AKT/NF-κB/VEGF pathway, GV1001 exhibits several potential biological mechanisms of action, with involvement in the TGF-β signaling pathway 25, the hypoxia-induced HIF-1α-VEGF signaling axis 19, and the ERK and p38 MAP kinase pathway 26. In addition, GV1001 inhibits gonadotropin-releasing hormone (GnRH) and 5α‑reductase, which are important in prostate cancer 27, 28. Kim et al reported that GV1001 can be a therapeutic agent for testosterone-induced benign prostatic hyperplasia (BPH) 27.…”

Section: Discussionmentioning

confidence: 75%

“…The authors found that GV1001 significantly decreased prostate weight and inhibited 5α‑reductase activity in a dose-dependent manner. GV1001 is a ligand for GnRH receptor to selectively stimulate the Gαs/cAMP pathway and antagonize Gαq-coupled Ca 2+ release by leuprolide acetate in prostate cancer 28. GV1001 might also exhibit anti-cancer effects in CRPC cells through these biological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

GV1001 inhibits cell viability and induces apoptosis in castration-resistant prostate cancer cells through the AKT/NF-κB/VEGF pathway

Park¹,

Jung²,

Kim³

et al. 2019

J. Cancer

View full text Add to dashboard Cite

Purpose: We examined the effect of GV1001 in castration castration-resistant prostate cancer (CRPC) cell growth and invasion and explored the potential molecular mechanisms of action.Materials and Methods: The in vitro anti-cancer effects of GV1001 in CRPC cells were examined using cell viability assay, TUNEL assay, and flow cytometry analysis. To evaluate the effects of GV1001 on different steps of angiogenesis, wound healing assay, transwell invasion assay, endothelial cell tube formation assay, and western blot analysis were performed. Finally, the anti-cancer effects of GV1001 on tumor growth in vivo were examined in a CRPC xenograft model.Results: GV1001 inhibited cell viability and induced apoptosis in CRPC cells in vitro, accompanied by down-regulation of Bcl-2 and caspase-3. GV1001 also inhibited different steps of angiogenesis, such as migration, invasion, and endothelial tube formation, along with decreased expression of MMP-2, MMP-9, and CD31 and increased expression of TIMP-1 and TIMP-2. Mechanistically, GV1001 significantly decreased the levels of phosphorylated AKT, phosphorylated p65, and VEGF in CRPC cells in a dose-dependent manner. GV1001 was effective in suppressing tumor growth and inducing apoptosis in a CRPC xenograft mouse model.Conclusions: Our data demonstrated that GV1001 inhibited cell viability, induced apoptosis, and inhibited angiogenesis in CRPC cells by inhibition of the AKT/NF-κB/VEGF signaling pathway.

show abstract

“…We recently reported that Gαs-cAMP signaling is selectively activated by GV1001 binding to GnRHR, but not by LA, a representative GnRHR agonist (22). We compared cAMP-dependent transcriptional activities of CA (a representative GnRHR antagonist), LA and GV1001 in GnRHR-overexpressing HEK293 cells.…”

Section: Resultsmentioning

confidence: 99%

“…GV1001, a 16 amino acid peptide derived from the human telomerase reverse transcriptase (hTERT), has been proposed as a cancer vaccine to boost immune responses of CD8 and CD4 T cells (21). We have recently demonstrated that GV1001 functions as a GnRHR ligand and selectively stimulates the Gαs-cAMP pathway (22). Although it has been proposed that GnRH analogs regulate not only well-established Gαq but also Gαs pathway in several extra-pituitary cells (23)(24)(25), pharmacological effects of Gαscoupled GnRHR activation has not been studied in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-Metastatic Effect of GV1001 on Prostate Cancer Cells; Roles of GnRHR-Mediated Gαs-cAMP Pathway and AR-YAP1 Axis

Kim

Park

Kim

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Gonadotropin-releasing hormone receptor (GnRHR) transmits its signal via two major Gα-proteins, primarily Gαq and Gαi. However, the precise mechanism underlying the functions of Gαs signal in prostate cancer cells is still unclear. We have previously identified that GV1001, a fragment of the human telomerase reverse transcriptase, functions as a biased GnRHR ligand to selectively stimulate the Gas/cAMP pathway. Here, we tried to reveal the potential mechanisms of which GV1001- stimulated Gαs-cAMP signaling pathway reduces the migration and metastasis of prostate cancer (PCa) cells.Methods: The expression of epithelial-mesenchymal transition (EMT)-related genes was measured by western-blotting and spheroid formation on ultra-low attachment plate was detected after GV1001 treatment. In vivo Spleen-liver metastasis mouse model was used to explore the inhibitory effect of GV1001 on metastatic ability of PCa and the transwell migration assay was performed to identify whether GV1001 had a suppressive effect on cell migration in vitro. In order to demonstrate the interaction between androgen receptor (AR) and YAP1, co-immunoprecipitation (co-IP), immunofluorescence (IF) staining, chromatin immunoprecipitation (ChIP) were performed in LNCaP cells with and without GV1001 treatment.Results: GV1001 inhibited expression of EMT-related genes and spheroid formation. GV1001 also suppressed in vivo spleen-liver metastasis of LNCaP cells as well as cell migration in vitro. GV1001 enhanced the phosphorylation of AR and transcription activity of androgen response element reporter gene through cAMP/protein kinase A pathway. Moreover, GV1001 increased Ser-127 phosphorylation of YAP1 and its ubiquitination, and subsequently decreased the levels of AR-YAP1 binding in the promoter region of the CTGF gene. In contrast, both protein and mRNA levels of NKX3.1 known for tumor suppressor gene and AR-coregulator were upregulated by GV1001 in LNCaP cells. YAP1 knockout using CRISPR/Cas9 significantly suppressed the migration ability of LNCaP cells, and GV1001 did not affect the cell migration of YAP1-deficient LNCaP cells. On the contrary, cell migration was more potentiated in LNCaP cells overexpressing YAP5SA, a constitutively active form of YAP1, which was not changed by GV1001 treatment. Conclusions: Overall, this study reveals an essential role of AR-YAP1 in the regulation of PCa cell migration, and provide evidence that GV1001 could be a novel GnRHR ligand to inhibit metastasis of PCa via the Gas/cAMP pathway.

show abstract

Anti-cancer effect of GV1001 for prostate cancer: function as a ligand of GnRHR

Cited by 14 publications

References 52 publications

Cold atmospheric plasma generated reactive species aided inhibitory effects on human melanoma cells: an in vitro and in silico study

Cold atmospheric plasma generated reactive species aided inhibitory effects on human melanoma cells: an in vitro and in silico study

GV1001 inhibits cell viability and induces apoptosis in castration-resistant prostate cancer cells through the AKT/NF-κB/VEGF pathway

Anti-Metastatic Effect of GV1001 on Prostate Cancer Cells; Roles of GnRHR-Mediated Gαs-cAMP Pathway and AR-YAP1 Axis

Contact Info

Product

Resources

About