{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:36:16Z","timestamp":1791196576084,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,3,8]],"date-time":"2002-03-08T00:00:00Z","timestamp":1015545600000},"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":[[2002,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multidrug resistance (MDR) mediated by the ATP\u2010dependent efflux protein P\u2010glycoprotein (P\u2010gp) is a major obstacle to the successful treatment of many cancers. In addition to effluxing toxins, P\u2010gp has been shown to protect tumor cells against caspase\u2010dependent apoptosis mediated by Fas and tumor necrosis factor receptor (TNFR) ligation, serum starvation and ultraviolet (UV) irradiation. However, P\u2010gp does not protect against caspase\u2010independent cell death mediated by granzyme B or pore\u2010forming proteins (perforin, pneumolysin and activated complement). We examined the effects of the chemotherapeutic hybrid polar compound suberoylanilide hydroxamic acid (SAHA) on P\u2010gp\u2010expressing MDR human tumor cell lines. In the CEM T\u2010cell line, SAHA, a histone deacetylase inhibitor, induced equivalent death in P\u2010gp\u2010positive cells compared with P\u2010gp\u2010negative cells. Cell death was marked by the caspase\u2010independent release of cytochrome c, reactive oxygen species (ROS) production and Bid cleavage that was not affected by P\u2010gp expression. However, consistent with our previous findings, SAHA\u2010induced caspase activation was inhibited in P\u2010gp\u2010expressing cells. These data provide evidence that P\u2010gp inhibits caspase activation after chemotherapeutic drug treatment and demonstrates that SAHA may be of value for the treatment of P\u2010gp\u2010expressing MDR cancers. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10327","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:45:33Z","timestamp":1030319133000},"page":"292-298","source":"Crossref","is-referenced-by-count":59,"title":["Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces cell death in P\u2010glycoprotein\u2010expressing cells"],"prefix":"10.1002","volume":"99","author":[{"given":"Astrid A.","family":"Ruefli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bernhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie 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