Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells

Abstract

Abstract. Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1-and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.

Histone Deacetylase (HDAC) Inhibition Induces IκB Kinase (IKK)-dependent Interleukin-8/CXCL8 Expression in Ovarian Cancer Cells

“…4). In addition, Sonnemann et al (60) have shown that HDIs and aspirin synergistically induce cell death in OC cells in vitro independent of cyclooxygenase. Because aspirin and other nonsteroidal anti-inflammatory drugs, in addition to inhibiting cyclooxygenase activity, inhibit IKK activity (41,61), it is possible that the observed HDI/aspirin synergistic effect was mediated by IKK inhibition and suppression of the IL-8 expression induced by HDAC inhibition.…”

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

“…18 TSA causes apoptosis through the inhibition of cell viability, as well as proliferation of cells expressing apoptosis-related proteins and activation of those proteins in a variety of cancer cells, including human breast, gastric, ovarian, small-cell lung, and cervical cancer cells. [19][20][21][22][23] TSA is not only a potential inducer of apoptosis but also involved in reprogramming efficiencies of stem cells. 24 Although several studies have reported that TSA has a potential inhibitory effect on cancer, there is limited information on the combination effect of TSA particularly with nanoparticles.…”

Prospected epigenetic moderators from natural sources and drug of class NSAIDS as effective treatment options to Prostate cancer

“…At the histone level, it has also been reported to induce and inhibit of deacetylases with direct acetylation of histones [131][132][133]. Studies has also reported Aspirin inhibiting AR related transcriptional activity in both androgen dependent and independent prostate cancer [134] while regulating the aberrant overexpression of AKR1C3 gene in certain breast cancer cell lines [135].…”