Nitric Oxide Donating Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Human Prostate Cancer Cell Systems and Human Prostatic Stroma via Caspase-3

Abstract

NO-NSAIDs are potent antiproliferative pro-apoptotic compounds in prostate cell systems. This pro-apoptotic effect is mediated via caspase-3 and it is independent of the type of prostate cell used. These findings have ramifications for the use of these new drugs in prostate cancer chemoprevention or treatment.

DNA strand breaks and hypoxia response inhibition mediate the radiosensitisation effect of nitric oxide donors on prostate cancer under varying oxygen conditions

“…This work complements and expands our previous studies which demonstrated the cytotoxic effects of NO-NSAIDs on prostate cancer cells under normoxia and hypoxia [6,7]. The use of both 2D and 3D models showed that NO-sulindac radiosensitised the PC-3 hormone insensitive prostate cancer cell line, not only under normoxia but particularly under chronic hypoxia.…”

“…NONSAIDs combine the anti-proliferative effects of NSAIDs with the gastric protection and potential tumouricidal effects of NO [3]. We and others have demonstrated that NO-NSAIDs prevent the development of malignancy and are powerful agents against established cancer deposits in vitro and in vivo [4][5][6]. Recently we have determined the function of NO-sulindac under hypoxic conditions and shown that this agent inhibits the hypoxia response in the PC-3 prostate cancer cell line via the Akt pathway [7].…”

Ultrastructure of Renal Tubular Epithelial Cells Of Rat’s Kidneys after Administration of L-Arginine

“…Other authors observed that NO inhibited proliferation and had proapoptotic effects on the epithelial cells of the prostate (15,22).…”

“…Various exogenous precursors of nitric oxide were used in the studies on the effects of NO on various tissues and organs in experimental animals, as well as humans (15), including non-steroidal anti-inflammatory drugs (NSAID), (22) so-called donors of nitric oxide (NO-NSAID) (15): NO-inbuprofen (NCX 2111), NOaspirin (NCX 4060) (22), and nitrosulindac (NCX 1102) (15). Other precursors of exogenous nitric oxide also included: sodium nitroprusside (SNP) (2), and S-nitroso-N-acethyl-penicylamine (SNAP) (19).…”

Synthesis of N-Pyridin-2-ylmethyl and N-Quinolin-2-ylmethyl ­Substituted Ethane-1,2-diamines

“…[9][10][11] Recent studies have shown that NO can reverse prostate cancer resistance to chemotherapy and radiotherapy, increase tumor response to anticancer drugs, and promote cancer cell death. [12][13][14][15][16][17] NO can prohibit prostate cancer cells from entering interstitial tissue and inhibit cancer cell invasion and transmission. 18,19 Many NO delivery compounds, both organic and inorganic, have been explored as suitable NO donors.…”