{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:54:50Z","timestamp":1785876890182,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multidrug resistance (MDR) remains a critical barrier in effective cancer chemotherapy which is largely attributed to the overexpression of ATP\u2010binding cassette (ABC) transporters. P\u2010glycoprotein (P\u2010gp) is the major ABC transporter which actively effluxes chemotherapeutic agents from cancer cells. In the present study, we investigated the effect of deinoxanthin (DNX), a carotenoid isolated from\n                    <jats:italic>Deinococcus radiodurans<\/jats:italic>\n                    , as a reversal agent of P\u2010gp\u2010mediated drug resistance. The structure of isolated DNX was confirmed using HPLC, spectroscopic analyses, and HRMS. Molecular docking studies revealed a favorable binding interaction between DNX and human P\u2010gp. Further, functional assays demonstrated that DNX significantly enhanced intracellular accumulation of Calcein\u2010AM in doxorubicin\u2010resistant MCF\u20107 (MCF\u20107\/DOX) cells in a concentration\u2010dependent manner. We observed that doxorubicin (DOX) alone treatment exhibited limited cytotoxicity in P\u2010gp overexpressing MDR cells. However, its combination with DNX markedly restored drug sensitivity, as evidenced by synergistic effects in combination index (CI) analysis. Additionally, DNX enhanced intracellular retention of DOX in the P\u2010gp overexpressing MDR cells. The DNX\u2010DOX combination also significantly reduced the migratory potential of MCF\u20107\/DOX cells compared to DOX alone treatment. It has also been noticed that DNX treatment attenuated P\u2010gp overexpression in the MDR cells. Further, DNX treatment suppressed interleukin\u20106 (IL\u20106) expression and modulates PI3K\/AKT\/NF\u2010\u03baB signaling pathway MDR cells. In conclusion, DNX significantly inhibits P\u2010gp drug efflux activity and indirectly suppress its expression most probably, through PI3K\/AKT\/NF\u2010\u03baB signaling modulation. These findings suggest that DNX as a P\u2010gp reversal candidate warranting further preclinical evaluation, including pharmacokinetic and in vivo studies, for the reversal of P\u2010gp\u2010mediated multidrug resistance in cancer.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70961","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:43:24Z","timestamp":1780922604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deinoxanthin Overcomes P\u2010Glycoprotein\u2010Mediated Multidrug Resistance in Breast Cancer Cells"],"prefix":"10.1002","volume":"40","author":[{"given":"Susithra","family":"Babu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology Annamalai University Chidambaram Tamil Nadu 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