Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole

Oncogene
Ahmed E GodaToshiyuki Sakai

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive cytokine that selectively targets cancer cells, however its efficacy has been challenged by a number of resistance mechanisms. Therefore, the current study investigated the potential of dipyridamole to enhance TRAIL efficacy and the probable underlying mechanisms. Dipyridamole dramatically sensitized p53-mutant human cancer cell lines: SW480, MG63 and DU145, to the antitumor activity of TRAIL, as evidenced by enabling TRAIL to efficiently cleave initiator and executioner caspases. Although dipyridamole upregulated both DR4 and DR5 and increased their cell surface expression, RNA interference revealed a preferential dependence on DR5. Moreover, dipyridamole inhibited survivin expression and its important consequences were confirmed by small interfering RNA. Mechanistically, dipyridamole induced transcriptional shutdown of survivin expression accompanying G(1) arrest that was characterized by downregulation of D-type cyclins and cdk6. In addition, a transcriptional mechanism powered by CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) induction was responsible for DR5 upregulation by dipyridamole. Importantly, dipyridamole-...Continue Reading

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Citations

Jun 25, 2009·Cancer Immunology, Immunotherapy : CII·Peter Hersey, Xu Dong Zhang
Mar 25, 2011·Environmental Health and Preventive Medicine·Tatsushi YoshidaToshiyuki Sakai
Sep 4, 2012·International Journal of Molecular Sciences·Carmine StolfiGiovanni Monteleone
Jul 5, 2012·Clinical & Experimental Metastasis·Daniela SpanoMassimo Zollo
Jan 20, 2016·American Journal of Reproductive Immunology : AJRI·Ayumi TaguchiYutaka Osuga
Jan 26, 2010·International Journal of Cancer. Journal International Du Cancer·Marie Laure PlissonnierIsabelle Lascombe
Apr 25, 2013·Biochemical Pharmacology·Ahmed E GodaToshiyuki Sakai
Apr 18, 2015·Frontiers in Oncology·Rachana Trivedi, Durga Prasad Mishra
May 10, 2018·Journal of Cellular Physiology·Reyhaneh Moradi MarjanehMajid Khazaei
Jul 15, 2017·Cancer Metastasis Reviews·P GreseleM Sebastiano
Jan 18, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Alaa E El-SisiSally E Abu-Risha

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