Abstract 1800: Inhibition of scavenger receptor class B type I suppresses androgen pathway activity and induces cytotoxic stress in C4-2 castration resistant prostate cancer cells

2016 ◽  
Author(s):  
Jacob A. Gordon ◽  
Ankur Midha ◽  
Mitali Pandey ◽  
Kishor Wasan ◽  
Michael E. Cox
Keyword(s):  
Prostate Cancer ◽  
Scavenger Receptor ◽  
Type I ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Pathway Activity ◽  
Castration Resistant ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Cytotoxic Stress

scholarly journals Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1509
Author(s):  
Mitali Pandey ◽  
Grace Cuddihy ◽  
Jacob A. Gordon ◽  
Michael E. Cox ◽  
Kishor M. Wasan
Keyword(s):  
Prostate Cancer ◽  
Scavenger Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Steroid Synthesis ◽  
Uptake Inhibition ◽  
Castration Resistant ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Expression And Activity

There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.

scholarly journals Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice

2020 ◽  
Vol 295 (24) ◽  
pp. 8252-8261 ◽  
Author(s):  
C. Alicia Traughber ◽  
Emmanuel Opoku ◽  
Gregory Brubaker ◽  
Jennifer Major ◽  
Hanxu Lu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cell ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Prostate Cancer Cells ◽  
Scavenger Receptor Class ◽  
Class B

High-density lipoprotein (HDL) metabolism is facilitated in part by scavenger receptor class B, type 1 (SR-B1) that mediates HDL uptake into cells. Higher levels of HDL have been associated with protection in other diseases, however, its role in prostate cancer is not definitive. SR-B1 is up-regulated in prostate cancer tissue, suggesting a possible role of this receptor in tumor progression. Here, we report that knockout (KO) of SR-B1 in both human and mouse prostate cancer cell lines through CRISPR/Cas9-mediated genome editing reduces HDL uptake into the prostate cancer cells and reduces their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 WT (SR-B1+/+) and SR-B1 KO (SR-B1−/−) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice revealed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1−/− prostate cancer cells formed smaller tumors in WT hosts than SR-B1+/+ cells in the same host model. Increased tumor volume was overall associated with reduced survival. We conclude that knocking out SR-B1 in prostate cancer tumors reduces HDL-associated increases in prostate cancer cell proliferation and disease progression.

scholarly journals HDL modification by secretory phospholipase A2 promotes scavenger receptor class B type I interaction and accelerates HDL catabolism

2000 ◽  
Vol 41 (11) ◽  
pp. 1849-1857 ◽  
Author(s):  
Frederick C. de Beer ◽  
Patrice M. Connell ◽  
J. Yu ◽  
Maria C. de Beer ◽  
Nancy R. Webb ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Scavenger Receptor ◽  
Type I ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ding-fang Zhang ◽  
Zhi-chun Yang ◽  
Jian-qiang Chen ◽  
Xiang-xiang Jin ◽  
Yin-da Qiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Adhesion ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Dna Damage And Repair ◽  
Castration Resistant

Abstract Background Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. Methods The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), β-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. Results The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. Conclusion Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

MS81 LIVER-SPECIFIC LIPOPLEXES FOR THE KNOCKDOWN OF SCAVENGER RECEPTOR CLASS B TYPE I

2010 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
K. Duwensee ◽  
I. Tancevski ◽  
E. Demetz ◽  
P. Eller ◽  
C. Heim ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B
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