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In this study, we examined the sensitizing property of andrographolide (Andro) to reverse MDR in the drug\u2010resistant KBCh<jats:sup>R<\/jats:sup> 8\u20105 cells. Andro exhibited increased cytotoxicity in a concentration\u2010dependent manner in the P\u2010gp overexpressing KBCh<jats:sup>R<\/jats:sup> 8\u20105 cells. Furthermore, Andro showed synergistic interactions with PTX and DOX in this drug\u2010resistant cells. Andro co\u2010administration enhanced PTX\u2010 and DOX\u2010induced cytotoxicity and reduced cell proliferation in the MDR cancer cells. Moreover, reactive oxygen species (ROS) were elevated with a decrease in the mitochondrial membrane potential (MMP) during Andro and chemotherapeutic drugs combination treatment in the drug\u2010resistant cells. Furthermore, Andro and PTX\u2010induced cell cycle arrest was observed in the drug\u2010resistant cell. We also noticed that the expression of ABCB1 and AKT were downregulated during Andro (4\u2009\u00b5M) treatment. Furthermore, Andro treatment enhanced the expression of caspase 3 and caspase 9 in the combinational groups that support the enhanced apoptotic cell death in drug\u2010resistant cancer cells. Therefore, the results reveal that Andro plays a role in the reversal of P\u2010gp\u2010mediated MDR in KBCh<jats:sup>R<\/jats:sup> 8\u20105 cells which might be due to regulating ABCB1\/AKT signaling pathway.<\/jats:p>","DOI":"10.1002\/cbf.3948","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:33:10Z","timestamp":1707352390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Andrographolide reverts multidrug resistance in KBCh<sup>R<\/sup> 8\u20105 cells through AKT signaling pathway"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4397","authenticated-orcid":false,"given":"Deepa S.","family":"Lakra","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology Annamalai University Annamalainagar Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradhapsingh","family":"Bharathiraja","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology Annamalai University Annamalainagar Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Dhanalakshmi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology Annamalai University Annamalainagar Tamil Nadu India"},{"name":"Department of Biochemistry Dharmapuram Gnanambigai Government Arts College for Women Mayiladuthurai Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3937-8735","authenticated-orcid":false,"given":"N. 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