A novel naproxen derivative capable of displaying anti-cancer and anti-migratory properties against human breast cancer cells

Abstract

BackgroundIncreasingly, the role of chronic inflammation and its mediators in tumor generation and progression is gaining importance in the field of cancer research. In this context, candidature of non steroidal anti-inflammatory drugs (NSAIDs) as potential anti-tumor therapeutic agent is being evaluated globally. In the present study we have evaluated the anti-cancer effect of a series of newly synthesized naproxen derivatives on human breast cancer cell lines.MethodsMCF-7 (poorly invasive) and MDA-MB-231 (highly invasive) cells were treated with different concentrations of naproxen sodium and its derivatives in vitro, and the underlying mechanism of action was monitored by employing studies related to induction of apoptosis, activation of caspases, cell-cycle progression, synthesis of PGE2 and cellular migration.ResultsAfter a preliminary screening using MCF-7 and MDA-MB-231 cells, it was evident that naproxen derivative 4 has a better killing property compared to its parent compound naproxen sodium (NS). On further investigation, it was apparent that the observed growth inhibitory activity on MDA-MB-231 cells after treatment with 4, was not due to cell cycle arrest but due to an early induction of apoptosis and subsequent induction of caspases 3 and 9. Derivative 4 could also inhibit COX activity in MDA-MB-231 cells as evidenced by reduction in prostaglandin E2 secretion. Moreover, 4 was capable of delaying the overall migration rate of MDA-MB-231 cells in vitro.ConclusionIn this study we report that a naproxen-derivative (4) has powerful anti-inflammatory and anti-tumor properties as it induces appreciable amount of apoptosis in breast cancer cell line, and can also delay migration of cancer cells (MDA-MB-231) which would in turn delay cancer cell invasion and formation of secondary tumours in primary breast cancer patients. Thus, we propose that 4 is worthy of further investigation due to its potential as a therapeutic agent in anti-tumor treatment regimen.

Anti‐tumor platinum (IV) complexes bearing the anti‐inflammatory drug naproxen in the axial position

“…On the other hand, a large number of studies have showed the effect of chronic inflammation in tumorgenesis, and the role of using non‐steroidal anti‐inflammatory drugs (NSAIDs) as anti‐cancer agents . Although the use of NSAIDs can cause some problems, such as gastrointestinal bleeding and increased cardiovascular (CV) issues, the anti‐inflammatory drug naproxen (Figure ) has fewer CV effects with a possible cardioprotective role in humans.…”

“…In addition, Deb et al . reported that some naproxen derivatives have powerful anti‐inflammatory and anti‐tumor properties as they induce an appreciable amount of apoptosis in the TNBC cell line …”

Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

“…[84] Progression and metastasis of cancer cells are relatedt ot he PGE 2 level. [86] Because NSAIDs are known to reduce inflammationb yi nhibiting COX enzymes that catalyze intracellular PGE 2 formation, [75] whichi se ffective and safe in ap hase II clinical trial against the growth and progression of prostatec ancer, [87] inhibiting cell migration of human breast cancer cells, [88] we have considered exploring the anticancer properties of these gelator salts. [86] Because NSAIDs are known to reduce inflammationb yi nhibiting COX enzymes that catalyze intracellular PGE 2 formation, [75] whichi se ffective and safe in ap hase II clinical trial against the growth and progression of prostatec ancer, [87] inhibiting cell migration of human breast cancer cells, [88] we have considered exploring the anticancer properties of these gelator salts.…”

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

“…Apart from improvements in solubility, derivatization of NAP also is known to enhance the anticancer activity. For example, IC 50 value of Naproxen sodium salt on MCF7 and MDA-MB-231 cell lines are >5 mM and ~10 mM respectively [68]. There is no consensus in the literature regarding the molecular mechanism of the anticancer activity of NSAIDs.…”