scholarly journals Sonlicromanol’s active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254315
Author(s):  
Xiaolan Jiang ◽  
Herma Renkema ◽  
Jan Smeitink ◽  
Julien Beyrath
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Active Metabolite ◽  
Treatment Approach ◽  
Prostaglandin E ◽  
Control Loop ◽  
Prostate Cancer Cells ◽  
Novel Treatment ◽  
Spheroid Growth ◽  
Elevated Expression

Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could affect prostate cancer cells-derived spheroid growth. We demonstrated that KH176m suppressed mPGES-1 expression and growth of DU145 (high mPGES-1 expression)-derived spheroids, while it had no effect on the LNCaP cell line, which has low mPGES-1 expression. By addition of exogenous PGE2, we found that the effect of KH176m on mPGES-1 expression and spheroid growth is due to the inhibition of a PGE2-driven positive feedback control-loop of mPGES-1 transcriptional regulation. Cancer stem cells (CSCs) are a subset of cancer cells exhibiting the ability of self-renewal, plasticity, and initiating and maintaining tumor growth. Our data shows that mPGES-1 is specifically expressed in this CSCs subpopulation (CD44+CD24-). KH176m inhibited the expression of mPGES-1 and reduced the growth of spheroids derived from the CSC. Based on the results obtained we propose selective mPGES-1 targeting by the sonlicromanol metabolite KH176m as a potential novel treatment approach for cancer patients with high mPGES-1 expression.

scholarly journals Transcriptomic profiling of docetaxel resistant prostate cancer cells and identification of novel treatment strategy

2013 ◽  
Vol 11 (8) ◽  
pp. 599-600
Author(s):  
Dara Lundon ◽  
Amanda O'Neill ◽  
Maria Prencipe ◽  
Sinead Ahearne ◽  
Padraig Doolan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Treatment Strategy ◽  
Prostate Cancer Cells ◽  
Transcriptomic Profiling ◽  
Novel Treatment

scholarly journals Hypoxia leads to significant changes in alternative splicing and elevated expression of CLK splice factor kinases in PC3 prostate cancer cells

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Elizabeth Bowler ◽  
Sean Porazinski ◽  
Simon Uzor ◽  
Philippe Thibault ◽  
Mathieu Durand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alternative Splicing ◽  
Cancer Cells ◽  
Splice Factor ◽  
Prostate Cancer Cells ◽  
Elevated Expression

scholarly journals Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy in vivo

2013 ◽  
Vol 5 (5) ◽  
pp. 1567-1571 ◽  
Author(s):  
KUN-HUANG YAN ◽  
YUNG-WEI LIN ◽  
CHI-HAO HSIAO ◽  
YU-CHING WEN ◽  
KE-HSUN LIN ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Treatment Strategy ◽  
Prostate Cancer Cells ◽  
Novel Treatment

scholarly journals MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 792 ◽  
Author(s):  
Takanori Eguchi ◽  
Thomas L. Prince ◽  
Manh Tien Tran ◽  
Chiharu Sogawa ◽  
Benjamin J. Lang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Heat Shock Protein 90 ◽  
Prostate Cancer Cells ◽  
Oncogenic Signaling ◽  
Normal Prostate ◽  
Elevated Expression ◽  
The Stability ◽  
Oncogenic Signaling Pathways

Cell division control 37 (CDC37) increases the stability of heat shock protein 90 (HSP90) client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SREZBP-CTfin51-AW1-Number 18 cDNA (SCAN) transcription factor family—MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1/ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced the tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in the CDC37 gene, negatively regulated the CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.

scholarly journals Polo-like Kinase 1 Facilitates Loss of Pten Tumor Suppressor-induced Prostate Cancer Formation

2011 ◽  
Vol 286 (41) ◽  
pp. 35795-35800 ◽  
Author(s):  
X. Shawn Liu ◽  
Bing Song ◽  
Bennett D. Elzey ◽  
Timothy L. Ratliff ◽  
Stephen F. Konieczny ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Prostate Cancer Cells ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Mouse Xenograft Model ◽  
Elevated Expression ◽  
Mitotic Stress

Loss of the tumor suppressor Pten (phosphatase and tensin homolog deleted on chromosome 10) is thought to mediate the majority of prostate cancers, but the molecular mechanism remains elusive. In this study, we demonstrate that Pten-depleted cells suffer from mitotic stress and that nuclear function of Pten, but not its phosphatase activity, is required to reverse this stress phenotype. Further, depletion of Pten results in elevated expression of Polo-like kinase 1 (Plk1), a critical regulator of the cell cycle. We show that overexpression of Plk1 correlates with genetic inactivation of Pten during prostate neoplasia formation. Significantly, we find that elevated Plk1 is critical for Pten-depleted cells to adapt to mitotic stress for survival and that reintroduction of wild-type Pten into Pten-null prostate cancer cells reduces the survival dependence on Plk1. We further show that Plk1 confers the tumorigenic competence of Pten-deleted prostate cancer cells in a mouse xenograft model. These findings identify a role of Plk1 in facilitating loss of Pten-induced prostate cancer formation, which suggests that Plk1 might be a promising target for prostate cancer patients with inactivating Pten mutations.

Elevated Expression of Hepatoma Up-Regulated Protein Inhibits γ-Irradiation-Induced Apoptosis of Prostate Cancer Cells

2015 ◽  
Vol 117 (6) ◽  
pp. 1308-1318 ◽  
Author(s):  
Mohamed Hassan ◽  
Abdelouahid El Khattouti ◽  
Ahmed Ejaeidi ◽  
Tangeng Ma ◽  
William A. Day ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Γ Irradiation ◽  
Elevated Expression ◽  
Induced Apoptosis

scholarly journals SCAND1 Suppresses CDC37 Gene Transcription by Repressing MZF1

2019 ◽  
Author(s):  
Takanori Eguchi ◽  
Thomas L. Prince ◽  
Tien Manh Tran ◽  
Chiharu Sogawa ◽  
Benjamin J. Lang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Gene Transcription ◽  
Cancer Progression ◽  
Prostate Cancer Cells ◽  
Oncogenic Signaling ◽  
Normal Prostate ◽  
Elevated Expression ◽  
The Stability ◽  
Oncogenic Signaling Pathways

Cell division control 37 (CDC37) increases the stability of HSP90 client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SCAN transcription factor family- MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1 / ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc-fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in CDC37 gene, negatively regulated CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.

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