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.
Highlights
The role of chronic inflammation and its mediators in tumor generation and progression is gaining importance in the field of cancer research
It is of note that prostaglandin E2 (PGE2), a known COX2-derived prostaglandin, plays a significant role in progression and metastasis of cancer cells by modulating local tumor microenvironment [12]
Treatment with 4 induces early apoptosis in MDA-MB-231 cells Because MDA-MB-231 is a highly aggressive cell line compared to MCF-7, we sought to study our compound of interest in depth using the former one
Summary
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. Since a vast number of studies have emphasized on the role of chronic inflammation in tumorogenesis [2] and potential use of nonsteroidal anti-inflammatory drugs (NSAID) as anti-cancer. It is of note that PGE2, a known COX2-derived prostaglandin, plays a significant role in progression and metastasis of cancer cells by modulating local tumor microenvironment [12]. Molecules with an enhanced capacity to reduce PGE2 in cancer cells are of great interest
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