{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:38:42Z","timestamp":1773099522863,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There have been conflicting reports of the apoptotic effects of nicotine on human cells and those studies reporting nicotine\u2010induced apoptosis have not unequivocally clarified the molecular mechanisms underlying the effect. However, we found here that human RSa cells, established from embryonic fibroblastic cells doubly infected with Rous sarcoma virus and Simian virus 40, underwent apoptosis when cultured with medium containing 0.06\u20130.6 \u03bcM nicotine. The apoptosis was assessed by cellular DNA fragmentation and caspase\u20103 protease activation. Viability of RSa cells was reduced by nicotine treatment, as analyzed by MTT assay and the reduction was lessened by combination treatment with a caspase\u20103 inhibitor, acetyl\u2010L\u2010aspartyl\u2010L\u2010glutamyl\u2010L\u2010valyl\u2010L\u2010aspart\u20101\u2010al (Ac\u2010DEVD\u2010CHO). Levels of expression of heat shock protein 90\u03b1 (Hsp90\u03b1) were found to be increased 20 min after the nicotine treatment, as analyzed by polymerase chain reaction\u2010based mRNA differential display after Northern blotting analysis of mRNA amounts. Cellular contents of Hsp90\u03b1 were furthermore increased in the nicotine\u2010treated RSa cells, as quantitated by Western immunoblot analysis. By contrast, in RSa cells treated with nicotine in combination with geldanamycin (GA), an inhibitor of Hsp90\u03b1 function, DNA fragmentation was not detected and caspase\u20103 protease activity levels were the same as those of mock\u2010treated cells. Nicotine\u2010induced caspase\u20103 activation and Hsp90\u03b1 expression, as well as suppression of the induction by GA, were also observed in a xeroderma pigmentosum patient\u2010derived cell line, XP2OS cells. Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90\u03b1 expression, in human cells tested. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10449","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:35:39Z","timestamp":1033907739000},"page":"37-42","source":"Crossref","is-referenced-by-count":31,"title":["Involvement of human heat shock protein 90\u03b1 in nicotine\u2010induced 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