Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Spange S, Wagner T, Heinzel T, Krämer OH. The fundamental role of epigenetic events in cancer. Smarter drugs emerging in pancreatic cancer therapy. Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells. Gilardini Montani MS, Granato M, Santoni C, Del Porto P, Merendino N, D’Orazi G, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2014.īray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Future studies are needed to clarify the role of LEF1 in this model. Our novel combined approach enabled specific, accurate and reproducible IC 50 calculation at single cell basis with no apparent effect on Wnt signaling components. In conclusion, cancer studies mostly utilize MTT or BrdU assays in estimating cell proliferation and calculating IC 50 of drugs, which provided conflicting VPA dosages utilizing PANC-1 cells. Among the screened Wnt components and target genes, only LEF1 exhibited significant four-fold upregulation at this concentration. Cell proliferation was inhibited by 50% at 2.5 mM VPA that evoked a significant apoptotic response. Taqman hydrolysis probes and SYBR Green PCR Mastermix were assessed in expression analyses of Wnt components utilizing 2 −ΔΔCt method. Flow cytometry measurements were analyzed by CellQuest and NovoExpress. Three independent proliferation and apoptosis assays were performed utilizing carboxyfluorescein succinimidyl ester and Annexin V/PI staining, respectively. PANC-1 was induced with increased VPA doses and time points. We aimed to calculate IC 50 of VPA-induced PANC-1 cells by combined analyses of proliferation and apoptosis, while assessing its effect on Wnt signaling pathway. However, VPA-induced apoptosis and its impact on Wnt signaling in PDACs are not linked, yet. Wnt signaling pathway is known to be involved in apoptosis and PDAC onset. Valproic acid (VPA) was shown to induce apoptosis and reduce proliferation in PANC-1 cells. Since most patients develop resistance to conventional treatments, new approaches are in urgency. Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly cancers.
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