Growth inhibitory effects of PC‑NSAIDs on human breast cancer subtypes in cell culture

Abstract

The potential role of non-steroidal anti-inflammatory drug (NSAID) therapy in the prevention and treatment of cancer has generated considerable research interest. Phosphatidylcholine (PC)-associated NSAIDs decrease the gastrointestinal side effects of NSAID therapy, and may be more effective than traditional NSAIDs in limiting tumor growth. In the present study, human cells representing three major breast cancer subtypes were cultured with aspirin, indomethacin and PC-associated forms of each drug, with PC alone as a control. All tested drugs decreased the tumor cell number after 8 days of culture, with PC-NSAIDs having the greatest inhibitory effect, and NSAIDs alone, particularly aspirin, having the least effect. PC alone was effective in limiting the proliferation of all cell lines, suggesting that the two components of PC-NSAIDs have an additive effect. The ELISA results did not support a strong role for inhibition of cyclooxygenase enzymes in the decrease in cancer cell proliferation, which may account for the limited effectiveness of aspirin alone. PC-NSAIDs, particularly indomethacin-PC, are attractive candidate drugs in the prevention and treatment of different types of breast cancer, including triple negative breast cancer.

Contribution of non-steroidal anti-inflammatory drugs to breast cancer treatment: In vitro and in vivo studies

“…The antitumor effects of NSAIDs in in vitro models are dose- and time-dependent, as shown in Table-1 . The most frequently observed phenomenon is decreased cell viability and/or proliferation [ 106 , 109 ]. Some studies have analyzed COX-2 and PGE2 to determine whether the anticancer effect is due to a specific disruption pathway [ 97 , 101 , 114 ].…”

“…Acetylsalicylic acid, celecoxib, meloxicam, piroxicam, and deracoxib were the most frequently tested NSAIDs in canine mammary cancer cell lines [103][104][105][106], whereas acetylsalicylic acid was the only NSAID evaluated in a feline and a murine mammary cancer cell line [102,107]. NSAIDs, along with natural compounds such as curcumin, luteolin, resveratrol, and phosphatidylcholine [96,[108][109][110], have been tested in isolation. More recently, NSAIDs modified with metal ions, such as copper [111], silver [111][112][113], and zinc [114], with organoantimony [115], and conjugated with other antiproliferative agents, such as mitochondriotropic agents (triphenylarsine and triphenylphosphine) [111,112] have also been investigated.…”