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Current Cancer Drug Targets

Author(s): Yoshiaki Sato, Hironori Yoshino*, Eichi Tsuruga and Ikuo Kashiwakura

DOI: 10.2174/1568009620666200115161717

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Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation

Page: [372 - 381] Pages: 10

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Abstract

Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface.

Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR.

Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed.

Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression.

Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.

Keywords: Apoptosis, Fas, Fas ligand, ionizing radiation, Poly(I:C), retinoic acid-inducible gene-I-like receptor.

Graphical Abstract

[1]
Mollinedo, F.; Gajate, C. Fas/CD95 death receptor and lipid rafts: new targets for apoptosis-directed cancer therapy. Drug Resist. Updat., 2006, 9(1-2), 51-73.
[http://dx.doi.org/10.1016/j.drup.2006.04.002] [PMID: 16687251]
[2]
Peter, M.E.; Hadji, A.; Murmann, A.E.; Brockway, S.; Putzbach, W.; Pattanayak, A.; Ceppi, P. The role of CD95 and CD95 ligand in cancer. Cell Death Differ., 2015, 22(4), 549-559.
[http://dx.doi.org/10.1038/cdd.2015.3] [PMID: 25656654]
[3]
Wajant, H. The Fas signaling pathway: More than a paradigm. Science, 2002, 296(5573), 1635-1636.
[http://dx.doi.org/10.1126/science.1071553] [PMID: 12040174]
[4]
Kaufmann, T.; Strasser, A.; Jost, P.J. Fas death receptor signalling: roles of Bid and XIAP. Cell Death Differ., 2012, 19(1), 42-50.
[http://dx.doi.org/10.1038/cdd.2011.121] [PMID: 21959933]
[5]
Kawaguchi, S.; Mineta, T.; Ichinose, M.; Masuoka, J.; Shiraishi, T.; Tabuchi, K. Induction of apoptosis in glioma cells by recombinant human Fas ligand. Neurosurgery, 2000, 46(2), 431-438.
[http://dx.doi.org/10.1097/00006123-200002000-00030] [PMID: 10690733]
[6]
Hamasu, T.; Inanami, O.; Asanuma, T.; Kuwabara, M. Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists. J. Radiat. Res. (Tokyo), 2005, 46(1), 103-110.
[http://dx.doi.org/10.1269/jrr.46.103] [PMID: 15802865]
[7]
Ifeadi, V.; Garnett-Benson, C. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways. PLoS One, 2012, 7(2) e31762
[http://dx.doi.org/10.1371/journal.pone.0031762] [PMID: 22389673]
[8]
Chang, G.C.; Hsu, S.L.; Tsai, J.R.; Liang, F.P.; Lin, S.Y.; Sheu, G.T.; Chen, C.Y. Molecular mechanisms of ZD1839-induced G1-cell cycle arrest and apoptosis in human lung adenocarcinoma A549 cells. Biochem. Pharmacol., 2004, 68(7), 1453-1464.
[http://dx.doi.org/10.1016/j.bcp.2004.06.006] [PMID: 15345335]
[9]
Yoneyama, M.; Fujita, T. Structural mechanism of RNA recognition by the RIG-I-like receptors. Immunity, 2008, 29(2), 178-181.
[http://dx.doi.org/10.1016/j.immuni.2008.07.009] [PMID: 18701081]
[10]
Kawai, T.; Takahashi, K.; Sato, S.; Coban, C.; Kumar, H.; Kato, H.; Ishii, K.J.; Takeuchi, O.; Akira, S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol., 2005, 6(10), 981-988.
[http://dx.doi.org/10.1038/ni1243] [PMID: 16127453]
[11]
Elion, D.L.; Cook, R.S. Harnessing RIG-I and intrinsic immunity in the tumor microenvironment for therapeutic cancer treatment. Oncotarget, 2018, 9(48), 29007-29017.
[http://dx.doi.org/10.18632/oncotarget.25626] [PMID: 29989043]
[12]
Wu, Y.; Wu, X.; Wu, L.; Wang, X.; Liu, Z. The anticancer functions of RIG-I-like receptors, RIG-I and MDA5, and their applications in cancer therapy. Transl. Res., 2017, 190, 51-60.
[http://dx.doi.org/10.1016/j.trsl.2017.08.004] [PMID: 28917654]
[13]
Besch, R.; Poeck, H.; Hohenauer, T.; Senft, D.; Häcker, G.; Berking, C.; Hornung, V.; Endres, S.; Ruzicka, T.; Rothenfusser, S.; Hartmann, G. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J. Clin. Invest., 2009, 119(8), 2399-2411.
[http://dx.doi.org/10.1172/JCI37155] [PMID: 19620789]
[14]
Yoshino, H.; Iwabuchi, M.; Kazama, Y.; Furukawa, M.; Kashiwakura, I. Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro. Oncol. Lett., 2018, 15(4), 4697-4705.
[http://dx.doi.org/10.3892/ol.2018.7867] [PMID: 29541243]
[15]
Sato, Y.; Yoshino, H.; Kazama, Y.; Kashiwakura, I. Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Mol. Med. Rep., 2018, 18(6), 5286-5294.
[http://dx.doi.org/10.3892/mmr.2018.9536] [PMID: 30320341]
[16]
Horton, J.K.; Siamakpour-Reihani, S.; Lee, C.T.; Zhou, Y.; Chen, W.; Geradts, J.; Fels, D.R.; Hoang, P.; Ashcraft, K.A.; Groth, J.; Kung, H.N.; Dewhirst, M.W.; Chi, J.T. FAS death receptor: A breast cancer subtype-specific radiation response biomarker and potential therapeutic target. Radiat. Res., 2015, 184(5), 456-469.
[http://dx.doi.org/10.1667/RR14089.1] [PMID: 26488758]
[17]
Sun, S.Y.; Yue, P.; Hong, W.K.; Lotan, R. Induction of Fas expression and augmentation of Fas/Fas ligand-mediated apoptosis by the synthetic retinoid CD437 in human lung cancer cells. Cancer Res., 2000, 60(22), 6537-6543.
[PMID: 11103825]
[18]
Fukushi, S.; Yoshino, H.; Yoshizawa, A.; Kashiwakura, I. p53-independent structure-activity relationships of 3-ring mesogenic compounds’ activity as cytotoxic effects against human non-small cell lung cancer lines. BMC Cancer, 2016, 16, 521.
[http://dx.doi.org/10.1186/s12885-016-2585-6] [PMID: 27456853]
[19]
Yoshino, H.; Konno, H.; Ogura, K.; Sato, Y.; Kashiwakura, I. Relationship between the regulation of caspase-8-mediated apoptosis and radioresistance in human THP-1-derived macrophages. Int. J. Mol. Sci., 2018, 19(10) E3154
[http://dx.doi.org/10.3390/ijms19103154] [PMID: 30322167]
[20]
Yoshino, H.; Kumai, Y.; Kashiwakura, I. Effects of endoplasmic reticulum stress on apoptosis induction in radioresistant macrophages. Mol. Med. Rep., 2017, 15(5), 2867-2872.
[http://dx.doi.org/10.3892/mmr.2017.6298] [PMID: 28447729]
[21]
Apetoh, L.; Ghiringhelli, F.; Tesniere, A.; Obeid, M.; Ortiz, C.; Criollo, A.; Mignot, G.; Maiuri, M.C.; Ullrich, E.; Saulnier, P.; Yang, H.; Amigorena, S.; Ryffel, B.; Barrat, F.J.; Saftig, P.; Levi, F.; Lidereau, R.; Nogues, C.; Mira, J.P.; Chompret, A.; Joulin, V.; Clavel-Chapelon, F.; Bourhis, J.; André, F.; Delaloge, S.; Tursz, T.; Kroemer, G.; Zitvogel, L. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med., 2007, 13(9), 1050-1059.
[http://dx.doi.org/10.1038/nm1622] [PMID: 17704786]
[22]
Deng, L.; Liang, H.; Xu, M.; Yang, X.; Burnette, B.; Arina, A.; Li, X.D.; Mauceri, H.; Beckett, M.; Darga, T.; Huang, X.; Gajewski, T.F.; Chen, Z.J.; Fu, Y.X.; Weichselbaum, R.R. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity, 2014, 41(5), 843-852.
[http://dx.doi.org/10.1016/j.immuni.2014.10.019] [PMID: 25517616]
[23]
Yoshino, H.; Saitoh, T.; Kozakai, M.; Kashiwakura, I. Effects of ionizing radiation on retinoic acid-inducible gene-I-like receptors. Biomed. Rep., 2015, 3(1), 59-62.
[http://dx.doi.org/10.3892/br.2014.377] [PMID: 25469248]
[24]
Duewell, P.; Steger, A.; Lohr, H.; Bourhis, H.; Hoelz, H.; Kirchleitner, S.V.; Stieg, M.R.; Grassmann, S.; Kobold, S.; Siveke, J.T.; Endres, S.; Schnurr, M. RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells. Cell Death Differ., 2014, 21(12), 1825-1837.
[http://dx.doi.org/10.1038/cdd.2014.96] [PMID: 25012502]
[25]
Chakraborty, M.; Abrams, S.I.; Camphausen, K.; Liu, K.; Scott, T.; Coleman, C.N.; Hodge, J.W. Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J. Immunol., 2003, 170(12), 6338-6347.
[http://dx.doi.org/10.4049/jimmunol.170.12.6338] [PMID: 12794167]
[26]
Chakraborty, M.; Abrams, S.I.; Coleman, C.N.; Camphausen, K.; Schlom, J.; Hodge, J.W. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res., 2004, 64(12), 4328-4337.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0073] [PMID: 15205348]
[27]
Fukazawa, T.; Fujiwara, T.; Morimoto, Y.; Shao, J.; Nishizaki, M.; Kadowaki, Y.; Hizuta, A.; Owen-Schaub, L.B.; Roth, J.A.; Tanaka, N. Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells. Oncogene, 1999, 18(13), 2189-2199.
[http://dx.doi.org/10.1038/sj.onc.1202561] [PMID: 10327065]
[28]
Liu, W.; Lin, Y.T.; Yan, X.L.; Ding, Y.L.; Wu, Y.L.; Chen, W.N.; Lin, X. Hepatitis B virus core protein inhibits Fas-mediated apoptosis of hepatoma cells via regulation of mFas/FasL and sFas expression. FASEB J., 2015, 29(3), 1113-1123.
[http://dx.doi.org/10.1096/fj.14-263822] [PMID: 25466893]
[29]
Mohamed, M.S.; Bishr, M.K.; Almutairi, F.M.; Ali, A.G. Inhibitors of apoptosis: clinical implications in cancer. Apoptosis, 2017, 22(12), 1487-1509.
[http://dx.doi.org/10.1007/s10495-017-1429-4] [PMID: 29067538]
[30]
Liu, W.H.; Hsiao, H.W.; Tsou, W.I.; Lai, M.Z. Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation. EMBO J., 2007, 26(6), 1660-1669.
[http://dx.doi.org/10.1038/sj.emboj.7601611] [PMID: 17318174]
[31]
Bilim, V.; Yuuki, K.; Itoi, T.; Muto, A.; Kato, T.; Nagaoka, A.; Motoyama, T.; Tomita, Y. Double inhibition of XIAP and Bcl-2 axis is beneficial for retrieving sensitivity of renal cell cancer to apoptosis. Br. J. Cancer, 2008, 98(5), 941-949.
[http://dx.doi.org/10.1038/sj.bjc.6604268] [PMID: 18283311]
[32]
Hekim, N.; Cetin, Z.; Nikitaki, Z.; Cort, A.; Saygili, E.I. Radiation triggering immune response and inflammation. Cancer Lett., 2015, 368(2), 156-163.
[http://dx.doi.org/10.1016/j.canlet.2015.04.016] [PMID: 25911239]
[33]
Takahashi, M.; Inanami, O.; Kubota, N.; Tsujitani, M.; Yasui, H.; Ogura, A.; Kuwabara, M. Enhancement of cell death by TNF α-related apoptosis-inducing ligand (TRAIL) in human lung carcinoma A549 cells exposed to x rays under hypoxia. J. Radiat. Res. (Tokyo), 2007, 48(6), 461-468.
[http://dx.doi.org/10.1269/jrr.07028] [PMID: 17895594]
[34]
Cacan, E.; Greer, S.F.; Garnett-Benson, C. Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases. Int. J. Oncol., 2015, 47(6), 2264-2275.
[http://dx.doi.org/10.3892/ijo.2015.3192] [PMID: 26458736]
[35]
Knight, J.C.; Scharf, E.L.; Mao-Draayer, Y. Fas activation increases neural progenitor cell survival. J. Neurosci. Res., 2010, 88(4), 746-757.
[PMID: 19830835]