{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:58:35Z","timestamp":1782860315368,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Education","award":["NRF-2022R1F1A1069376"],"award-info":[{"award-number":["NRF-2022R1F1A1069376"]}]},{"name":"Basic Science Research Program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Education","award":["2024-0046"],"award-info":[{"award-number":["2024-0046"]}]},{"name":"Soonchunhyang University","award":["NRF-2022R1F1A1069376"],"award-info":[{"award-number":["NRF-2022R1F1A1069376"]}]},{"name":"Soonchunhyang University","award":["2024-0046"],"award-info":[{"award-number":["2024-0046"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Dysregulated cellular metabolism is known to be associated with drug resistance in cancer treatment. Methods: In this study, we investigated the impact of cellular adaptation to lactic acidosis on intracellular energy metabolism and sensitivity to docetaxel in prostate carcinoma (PC) cells. The effects of curcumin and the role of hexokinase 2 (HK2) in this process were also examined. Results: PC-3AcT and DU145AcT cells that preadapted to lactic acid displayed increased growth behavior, increased dependence on glycolysis, and reduced sensitivity to docetaxel compared to parental PC-3 and DU145 cells. Molecular analyses revealed activation of the c-Raf\/MEK\/ERK pathway, upregulation of cyclin D1, cyclin B1, and p-cdc2Thr161, and increased levels and activities of key regulatory enzymes in glycolysis, including HK2, in lactate-acclimated cells. HK2 knockdown resulted in decreased cell growth and glycolytic activity, decreased levels of complexes I\u2013V in the mitochondrial electron transport chain, loss of mitochondrial membrane potential, and depletion of intracellular ATP, ultimately leading to cell death. In a xenograft animal model, curcumin combined with docetaxel reduced tumor size and weight, induced downregulation of glycolytic enzymes, and stimulated the upregulation of apoptotic and necroptotic proteins. This was consistent with the in vitro results from 2D monolayer and 3D spheroid cultures, suggesting that the efficacy of curcumin is not affected by docetaxel. Conclusions: Overall, our findings suggest that metabolic plasticity through enhanced glycolysis observed in lactate-acclimated PC cells may be one of the underlying causes of docetaxel resistance, and targeting glycolysis by curcumin may provide potential for drug development that could improve treatment outcomes in PC patients.<\/jats:p>","DOI":"10.3390\/nu16244338","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T10:08:53Z","timestamp":1734343733000},"page":"4338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Curcumin and Its Potential to Target the Glycolytic Behavior of Lactate-Acclimated Prostate Carcinoma Cells with Docetaxel"],"prefix":"10.3390","volume":"16","author":[{"given":"Dongsic","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Gi","family":"Lee","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Marquette University, Milwaukee, WI 53233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7987","authenticated-orcid":false,"given":"Su-Hak","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Medicinal Bioscience, College of Biomedical and Health Science, Konkuk University Glocal Campus, Chungju 27478, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Kyen","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Seon","family":"Nam","sequence":"additional","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-1284","authenticated-orcid":false,"given":"Yoon-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1113\/JP278810","article-title":"Revisiting the Warburg effect: Historical dogma versus current understanding","volume":"599","author":"Vaupel","year":"2021","journal-title":"J. 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