The reported research examined the ability of exisulind (Aptosyn), CP461, CP248 and sulindac sulfide to inhibit growth and induce apoptosis in prostate cancer cell lines, irrespective of bcl-2 over-expression, androgen-dependence, or cyclooxygenase (COX) expression. The researchers showed that with doses that induced apoptosis, exisulind (Aptosyn), CP248, and CP461 reduced cellular PSA expression and decreased the secretion of PSA from androgen-dependent LNCaP cells. At the same time, PSA levels of LNCaP cells treated with aspirin remained elevated. In addition, cells treated with exisulind (Aptosyn) showed a decreased activity and expression of the androgen receptor.
Exisulind (Aptosyn) is the first product candidate from a novel class of compounds under development by Cell Pathways, called selective apoptotic anti-neoplastic drugs (SAANDs). SAANDs inhibit cyclic GMP phosphodiesterase and selectively induce apoptosis (programmed cell death) in abnormally growing precancerous and cancerous cells. Because SAANDs do not induce apoptosis in normal cells, they do not produce the serious side effects normally associated with traditional chemotherapeutic agents. They also do not inhibit cyclooxygenase (COX I or COX II) and have not exhibited the gastric and renal toxicities reported to be associated with non-steroidal anti-inflammatory drugs (NSAIDs), including the COX II specific inhibitors. A New Drug Application for exisulind (Aptosyn) as a treatment for patients with familial adenomatous polyposis, a precancerous condition tha
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