ATH 25.0% 0.5¢ alterity therapeutics limited

Copper as a target for prostate cancer therapeutics:...

  1. 1,847 Posts.
    lightbulb Created with Sketch. 1
    Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution
    Delphine Denoyer, et al.
    www.impactjournals.com/oncotarget
    Oncotarget, Advance Publications 2016

    ABSTRACT
    Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII (gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate denocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating enocarcinoma development. Implications for current clinical trials are discussed.
 
watchlist Created with Sketch. Add ATH (ASX) to my watchlist
(20min delay)
Last
0.5¢
Change
0.001(25.0%)
Mkt cap ! $26.19M
Open High Low Value Volume
0.5¢ 0.5¢ 0.5¢ $27.94K 6.050M

Buyers (Bids)

No. Vol. Price($)
47 58163299 0.4¢
 

Sellers (Offers)

Price($) Vol. No.
0.5¢ 57489001 48
View Market Depth
Last trade - 16.10pm 28/03/2024 (20 minute delay) ?
Last
0.5¢
  Change
0.001 ( 0.00 %)
Open High Low Volume
0.5¢ 0.5¢ 0.5¢ 20524121
Last updated 15.46pm 28/03/2024 ?
ATH (ASX) Chart
arrow-down-2 Created with Sketch. arrow-down-2 Created with Sketch.