Nonsteroidal anti-inlammatory drugs (NSAIDs) are commonly used as anti-inlammatory and analgesic agents. This family of drugs suppresses prostaglandin synthesis through inhibition of cyclooxygenase (COX) enzymes. Recent studies displayed that anti-carcinogenic actions of these drugs are mediated by COX-2 enzyme. Currently, there is intense research on COX-2 inhibitors as therapeutic targets. Etodolac is not perfectly selective but shows 'preferential selectivity' for COX-2. Here, in this study, we wanted to take gene expression snapshots of several apoptotic proteins under diferent conditions of drug exposure. The aim, therefore, focused to determine diferential efects of etodolac on the regulation of apoptotic genes in hormone-responsive MCF-7 and triple-negative MDA-MB-231 cancer cell lines. Our data suggest that MDA-MB-231 is more responsive to etodolac exposure. Cell proliferation and apoptosis consistently regulated upon drug addiction. Furthermore, COX-2/HER2 was explicitly an up-regulated, phosphorylated form of Bad accumulated and anti-apoptotic proteins SAG and survivin increased in both transcriptional and translational levels. Changes in mitochondrial Bcl-2 family proteins were moderate and pro-and anti-apoptotic proteins showed similar levels of regulation in both cell lines. We believe that these indings would be supportive for future studies targeting etodolac-based therapies, as it reveals apoptotic factors diferentially regulated in hormone-responsive and invasive cell lines.Keywords: apoptosis, MCF-7, MDA-MB-231, MTT, Bad, SAG © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
IntroductionNonsteroidal anti-inlammatory drugs (NSAIDs), regularly used for their anti-inlammatory and analgesic efects, were shown to have potency for cancer prevention as well [1,2]. This family of drugs suppresses prostaglandin synthesis through inhibition of cyclooxygenase (COX) enzymes. COX enzymes have two isoforms COX-1 and COX-2, with a recent addition of a splice variant of COX-1, COX-3, which is not functional in humans. COX-1 is commonly expressed in body, showing constitutive activation. COX-2, on the other hand, is hardly detectable in normal conditions but is induced upon stimulation by mitogenic agents, cytokines, growth factors, and so on. Later reports, however, demonstrated that COX-2 is also constitutively expressed in basal levels at several tissues including gastric mucosa, developing brain or kidney [3][4][5].COX isoforms catalyse prostaglandin G/H (PGG2/PGH2) synthesis from arachidonic acid, and these prostaglandins are then converted to stable forms like PGD2, PGE2, PGF2, prostacyclin (PGI2) or thromboxane A2 (TXA2) depending on the cell type. Inhibition of COX enzymes, therefore, could result in improper prostaglandin activity, which in turn may ca...
