{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:57:43Z","timestamp":1777701463454,"version":"3.51.4"},"reference-count":26,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    Melanoma differentiation-associated gene-7 (\n                    <jats:italic toggle=\"yes\">mda-7<\/jats:italic>\n                    )\/interleukin-24 (IL-24) induces caspase-3 cleavage and subsequent activation via the intrinsic or extrinsic pathway to result in cancer cell-selective apoptosis, but whether\n                    <jats:italic toggle=\"yes\">mda-7<\/jats:italic>\n                    \/IL-24 may directly regulate caspase-3 through the post-translational modification remains unknown. Here, we reported that tumor-selective replicating adenovirus ZD55-IL-24 led to caspase-3 denitrosylation and subsequent activation, indicating that caspase-3 denitrosylation played a crucial role in ZD55-IL-24-induced cancer cell apoptosis. To confirm the relationship between caspase-3 denitrosylation and its activation in response to ZD55-IL-24, we treated carcinoma cells with the different nitric oxide (NO) regulators to modulate caspase-3 denitrosylation level, then observed the corresponding caspase-3 cleavage. We found that NO inhibitor 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO) promoted caspase-3 denitrosylation and caspase-3 cleavage, thereby exacerbating ZD55-IL-24-induced cancer cell apoptosis, whereas NO donor sodium nitroprusside (SNP) showed the opposite effect. Moreover, caspase-3 denitrosylation facilitated its downstream target poly ADP-ribose polymerase (PARP) degradation that further increased the apoptotic susceptibility. Although caspase-3 activation controlled by denitrosylation modification has emerged as an important regulator of programmed cell death, the detailed molecular mechanism by which caspase-3 exerts its denitrosylation modification in response to ZD55-IL-24 still needs to be elucidated. Thus, our results demonstrated that ZD55-IL-24 increased Fas expression to enhance thioredoxin reductase 2 (TrxR2), which was responsible for caspase-3 denitrosylation. Collectively, these findings elucidate that ZD55-IL-24 induces caspase-3 denitrosylation through Fas-mediated TrxR2 enhancement, thereby facilitating caspase-3 cleavage and the downstream caspase signaling pathway activation, which provides a novel insight into ZD55-IL-24-induced cancer-specific apoptosis by post-translational modification of the apoptotic executor caspase-3.\n                  <\/jats:p>","DOI":"10.1089\/jir.2014.0061","type":"journal-article","created":{"date-parts":[[2014,10,27]],"date-time":"2014-10-27T14:15:22Z","timestamp":1414419322000},"page":"157-167","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Melanoma Differentiation Associated Gene-7\/Interleukin-24 Induces Caspase-3 Denitrosylation to Facilitate the Activation of Cancer Cell Apoptosis"],"prefix":"10.1177","volume":"35","author":[{"given":"Hui","family":"Tian","sequence":"first","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Fu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian-Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Sheng","family":"Pei","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Nian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xuzhou Medical College","place":["P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,3,1]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158265"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2764"},{"issue":"70","key":"e_1_3_3_5_1","first-page":"233","article-title":"Caspase activation","author":"Boatright KM","year":"2003","unstructured":"Boatright KM, , Salvesen GS. 2003. Caspase activation. Biochem Soc Symp (70):233\u2013242.","journal-title":"Biochem Soc Symp"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.22932"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2004.01.017"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.4.1069"},{"issue":"4","key":"e_1_3_3_9_1","first-page":"S23","article-title":"mda-7\/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic","volume":"2","author":"Fisher PB","year":"2003","unstructured":"Fisher PB, , Gopalkrishnan RV, , Chada S, , Ramesh R, , Grimm EA, , Rosenfeld MR, , Curiel DT, , Dent P. 2003. mda-7\/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic. Cancer Biol Ther, 2(4 Suppl 1):S23\u201337.","journal-title":"Cancer Biol Ther"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3758"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600210"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80551-8"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81873-5"},{"issue":"12","key":"e_1_3_3_14_1","first-page":"2477","article-title":"Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression","volume":"11","author":"Jiang H","year":"1995","unstructured":"Jiang H, , Lin JJ, , Su ZZ, , Goldstein NI, , Fisher PB. 1995. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene, 11(12):2477\u20132486.","journal-title":"Oncogene"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00245.x"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.08.012"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46817-4_22"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.651"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1315"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401847"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.11.6823"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207523"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00074-6"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878464"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2012.08.004"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606528103"},{"issue":"2","key":"e_1_3_3_27_1","first-page":"437","article-title":"mda-7\/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic reticulum stress","volume":"20","author":"Zhang X","year":"2008","unstructured":"Zhang X, , Kang X, , Shi L, , Li J, , Xu W, , Qian H, , Wu M, , Yin Z. 2008. mda-7\/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic reticulum stress. 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