{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:02:16Z","timestamp":1776949336226,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program","award":["R114-042"],"award-info":[{"award-number":["R114-042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Curcumin, a dietary polyphenol with anticancer potential, has been reported to enhance the efficacy of chemotherapeutic agents. Methods: The effects of combined curcumin and doxorubicin treatment on apoptosis and associated signaling pathways were investigated in human osteosarcoma HOS cells. Results: Combined treatment significantly reduced cell viability and induced apoptotic morphological changes, which were confirmed by increased sub-G1 population, enhanced DNA fragmentation, and elevated cleaved poly(ADP-ribose) polymerase (PARP) levels. Mechanistically, combined treatment markedly increased c-Jun N-terminal kinase (JNK) phosphorylation, whereas extracellular signal-regulated kinase (ERK) phosphorylation showed no appreciable change. Pharmacological inhibition revealed that JNK suppression attenuated PARP cleavage, while ERK inhibition also reduced apoptotic responses, suggesting a permissive role of basal ERK activity. In addition, combined treatment was associated with increased expression of the endoplasmic reticulum stress marker GRP78 and modulation of autophagy-associated markers. Although thioredoxin domain-containing protein 5 (TXNDC5) expression was reduced, TXNDC5 overexpression failed to attenuate apoptosis, indicating that apoptosis induction occurs independently of TXNDC5. Conclusions: These findings indicate that combined curcumin and doxorubicin induce apoptosis primarily through JNK-dependent MAPK signaling, accompanied by stress-associated cellular responses.<\/jats:p>","DOI":"10.3390\/nu18081235","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:47:02Z","timestamp":1776181622000},"page":"1235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Curcumin and Doxorubicin Induce Apoptosis via JNK-Dependent MAPK Signaling Independent of TXNDC5 in Human Osteosarcoma Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Yu-Hsiang","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, No. 539, Zhongxiao Rd., East Dist., Chiayi City 60002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-9166","authenticated-orcid":false,"given":"Kai-Chien","family":"Yang","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Section 1, Taipei City 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng-Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, A25-303 Room, Life Sciences Hall, No. 300, Syuefu Road, Chiayi City 600355, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Wei","family":"Shih","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Cheng","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, A25-303 Room, Life Sciences Hall, No. 300, Syuefu Road, Chiayi City 600355, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyun-Yu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chang Gung Memorial Hospital at Chiayi, No. 8, West Section of Jiapu Road, Puzi City, Chiayi County 613016, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fung-Jou","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, No. 110, Section 1, Jianguo North Road, Taichung City 402306, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang-Tzu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Clinical Microscopy, Cathay General Hospital, No. 280, Renai Rd., Sec. 4, Taipei City 106438, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-7116","authenticated-orcid":false,"given":"Ching-Hsein","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, A25-303 Room, Life Sciences Hall, No. 300, Syuefu Road, Chiayi City 600355, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Giacomini, I., Cortini, M., Tinazzi, M., Baldini, N., Cocetta, V., Ragazzi, E., Avnet, S., and Montopoli, M. 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