{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:11:49Z","timestamp":1776813109106,"version":"3.51.2"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEXT KAKENHI","award":["17H04725"],"award-info":[{"award-number":["17H04725"]}]},{"name":"MEXT KAKENHI","award":["21K11676"],"award-info":[{"award-number":["21K11676"]}]},{"name":"MEXT KAKENHI","award":["24K14724"],"award-info":[{"award-number":["24K14724"]}]},{"name":"MEXT KAKENHI","award":["20H02933"],"award-info":[{"award-number":["20H02933"]}]},{"name":"MEXT KAKENHI","award":["23H02161"],"award-info":[{"award-number":["23H02161"]}]},{"name":"MEXT KAKENHI","award":["23K26854"],"award-info":[{"award-number":["23K26854"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC\u2013glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC\u2013GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses.<\/jats:p>","DOI":"10.3390\/ijms26178145","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"8145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line"],"prefix":"10.3390","volume":"26","author":[{"given":"Ruitong","family":"Sun","sequence":"first","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"},{"name":"School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina","family":"Yano","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Satoh","sequence":"additional","affiliation":[{"name":"Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shintaro","family":"Munemasa","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"},{"name":"Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-1903","authenticated-orcid":false,"given":"Yoshiyuki","family":"Murata","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"},{"name":"Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5729-972X","authenticated-orcid":false,"given":"Toshiyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"},{"name":"Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-9105","authenticated-orcid":false,"given":"Yoshimasa","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan"},{"name":"Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125118","DOI":"10.1016\/j.foodchem.2019.125118","article-title":"Characterization of benzyl isothiocyanate extracted from mashed green papaya by distillation","volume":"299","author":"Nakamura","year":"2019","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1271\/bbb.90731","article-title":"Electrophiles in foods: The current status of isothiocyanates and their chemical biology","volume":"74","author":"Nakamura","year":"2010","journal-title":"Biosci. 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