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Immunotherapy targeting IDO1 has been one of the focus areas in cancer biology, but lately studies have identified non-immune related functions of IDO1 leading to a paradigm shift with regard to IDO1 function in the context of tumor cells. In this study, we show that PDAC tissues and PDAC cells overexpress IDO1. The expression level is reciprocally related to overall patient survival. We further show that carbidopa, an FDA-approved drug for Parkinson's disease as well as an AhR agonist, inhibits IDO1 expression in PDAC cells. Using athymic nude mice, we demonstrate that carbidopa-mediated suppression of IDO1 expression attenuates tumor growth. Mechanistically, we show that AhR is responsible for carbidopa-mediated suppression of IDO1, directly as a transcription factor and indirectly by interfering with the JAK\/STAT pathway. Overall, targeting IDO1 not only in immune cells but also in cancer cells could be a beneficial therapeutic strategy for PDAC and potentially for other cancers as well and that carbidopa could be repurposed to treat cancers that overexpress IDO1.<\/jats:p>","DOI":"10.1042\/bcj20210851","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T06:00:04Z","timestamp":1661234404000},"page":"1807-1824","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Carbidopa, an activator of aryl hydrocarbon receptor, suppresses IDO1 expression in pancreatic cancer and decreases tumor growth"],"prefix":"10.1042","volume":"479","author":[{"given":"Ksenija","family":"Korac","sequence":"first","affiliation":[{"name":"1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devaraja","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Sniegowski","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7120-2537","authenticated-orcid":false,"given":"Bradley K.","family":"Schniers","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"2Department of Biological Sciences, Texas Tech University, Lubbock, TX 79410, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-075X","authenticated-orcid":false,"given":"Yangzom D.","family":"Bhutia","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"2022090612301636700_BCJ-2021-0851C1","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1096\/fasebj.5.11.1907934","article-title":"Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism","volume":"5","year":"1991","journal-title":"FASEB J"},{"key":"2022090612301636700_BCJ-2021-0851C2","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.18632\/oncotarget.27646","article-title":"Indoximod opposes the immunosuppressive effects mediated by IDO and TDO via modulation of AhR function and activation of mTORC1","volume":"11","year":"2020","journal-title":"Oncotarget"},{"key":"2022090612301636700_BCJ-2021-0851C3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jri.2003.11.002","article-title":"Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance","volume":"61","year":"2004","journal-title":"J. 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