{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:59:02Z","timestamp":1773802742800,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T00:00:00Z","timestamp":1443398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan, ROC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zuoying Branch of Kaohsiung Armed Forces General Hospital","award":["103-2320-B-110-002-MY2"],"award-info":[{"award-number":["103-2320-B-110-002-MY2"]}]},{"name":"Zuoying Branch of Kaohsiung Armed Forces General Hospital","award":["104-24"],"award-info":[{"award-number":["104-24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>The primary cause of treatment failures in acute myeloid leukemia is usually associated with defects in the apoptotic pathway. Several studies suggest that 2\u2010(4\u2010aminophenyl)\u20107\u2010methoxybenzothiazole (7\u2010OMe\u2010APBT) may potentially induce apoptosis of cancer cells. Thus, the present study was conducted to explore the cytotoxic effect of 7\u2010OMe\u2010APBT on human leukemia U937 cells. The apoptosis of human leukemia U937 cells induced by 7\u2010OMe\u2010APBT was characterized by an increase in mitochondrial membrane depolarization, procaspase\u20108 degradation, and tBid production. Down\u2010regulation of FADD blocked 7\u2010OMe\u2010APBT\u2010induced procaspase\u20108 degradation and rescued the viability of 7\u2010OMe\u2010APBT\u2010treated cells, suggesting the involvement of a death receptor\u2010mediated pathway in 7\u2010OMe\u2010APBT\u2010induced cell death. Increased TNF\u2010\u03b1 expression, TNFR2 expression, and p38 MAPK phosphorylation were noted in 7\u2010OMe\u2010APBT\u2010treated cells. Pretreatment with a p38 MAPK inhibitor abolished 7\u2010OMe\u2010APBT\u2010induced TNF\u2010\u03b1 and TNFR2 up\u2010regulation. 7\u2010OMe\u2010APBT stimulated p38 MAPK\/c\u2010Jun\u2010mediated transcriptional up\u2010regulation of TNFR2, while the increased TNF\u2010\u03b1 mRNA stability led to TNF\u2010\u03b1 up\u2010regulation in 7\u2010OMe\u2010APBT\u2010treated cells. Treatment with 7\u2010OMe\u2010APBT up\u2010regulated protein phosphatase 2A catalytic subunit \u03b1 (PP2Ac\u03b1) expression via the p38 MAPK\/c\u2010Jun\/ATF\u20102 pathway, which, in turn, promoted tristetraprolin (TTP) degradation. Pretreatment with a protein phosphatase 2A inhibitor or TTP over\u2010expression abrogated TNF\u2010\u03b1 up\u2010regulation in 7\u2010OMe\u2010APBT\u2010treated cells. Abolishment of TNF\u2010\u03b1 up\u2010regulation or knock\u2010down of TNFR1\/TNFR2 by siRNA restored the viability of 7\u2010OMe\u2010APBT\u2010treated cells. Taken together, our data indicate a connection between p38 MAPK\u2010mediated TNF\u2010\u03b1 and TNFR2 up\u2010regulation and 7\u2010OMe\u2010APBT\u2010induced TNF\u2010\u03b1\u2010mediated death pathway activation in U937 cells. The same pathway also elucidates the mechanism underlying 7\u2010OMe\u2010APBT\u2010induced death of human leukemia HL\u201060 cells. J. Cell. Physiol. 230: 130\u2013141, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25064","type":"journal-article","created":{"date-parts":[[2015,6,9]],"date-time":"2015-06-09T16:50:37Z","timestamp":1433868637000},"page":"130-141","source":"Crossref","is-referenced-by-count":8,"title":["The Association Between p38 MAPK\u2010Mediated TNF\u2010\u03b1\/TNFR2 up\u2010Regulation and 2\u2010(4\u2010Aminophenyl)\u20107\u2010Methoxybenzothiazole\u2010Induced Apoptosis in Human Leukemia U937 Cells"],"prefix":"10.1002","volume":"231","author":[{"given":"Chia\u2010Hui","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences National Sun Yat\u2010Sen University Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences National Sun Yat\u2010Sen University Kaohsiung 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