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Curcumin has been reported in osteosarcoma therapy and bone regeneration, yet its suppressive mechanism remains unclear. Conventional views attribute curcumin’s effects to NRF2 activation and antioxidase gene upregulation that counter excess ROS, but the study shows curcumin increases intracellular ROS, damages DNA, and triggers apoptosis in MG-63 cells despite elevated NRF2 and related antioxidant gene expression.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/paradox-curcumin-a-natural-antioxidant-suppresses-osteosarcoma-cells-via-excessive-reactive-oxygen-species/383932/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/paradox-curcumin-a-natural-antioxidant-suppresses-osteosarcoma-cells-via-excessive-reactive-oxygen-species/383932.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are extended surgical resections used for osteosarcoma, and what complication can follow?","Question",{"text":113,"@type":114},"Extended resections are common to prevent local recurrence, but they can cause critical-size bone defects. 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Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species. Int. J. Mol. Sci. 2023, 24, 11975 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241511975  \nAcademic Editor: Claudio Di Cristofano  \nReceived: 28 June 2023  \nRevised: 18 July 2023  \nAccepted: 25 July 2023  \nPublished: 26 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, 1081 LA Amsterdam, The Netherlands; [c.xu@acta.nl](c.xu@acta.nl) (C.X.);  \n[m.wang@acta.nl](m.wang@acta.nl) (M.W.); [bzandiehdoulabi@acta.nl](bzandiehdoulabi@acta.nl) (B.Z.D.); [y.sun@acta.nl](y.sun@acta.nl) (Y.S.)  \n* [Correspondence: y.liu@acta.nl](Correspondence: y.liu@acta.nl)  \nAbstract: Osteosarcoma (OS) is an aggressive tumor with a rare incidence. Extended surgical resections are the prevalent treatment for OS, which may cause critical-size bone defects. These bone defects lead to dysfunction, weakening the post-surgical quality of patients' life. Hence, an ideal therapeutic agent for OS should simultaneously possess anti-cancer and bone repair capacities. Curcumin (CUR) has been reported in OS therapy and bone regeneration. However, it is not clear how CUR suppresses OS development. Conventionally, CUR is considered a natural antioxidant inline with its capacity to promote the nuclear translocation of a nuclear transcription factor, nuclear factor erythroid 2 (NRF2) . After nuclear translocation, NRF2 can activate the transcription of some antioxidases, thereby circumventing excess reactive oxygen species (ROS) that are deleterious to cells. Intriguingly, this research demonstrated that, in vitro, 10 and 20 􀀖M CUR increased the intracellular ROS in MG-63 cells, damaged cells' DNA, and finally caused apoptosis of MG-63 cells, although increased NRF2 protein level and the expression of NRF2-regulated antioxidase genes were identified in those two groups.  \nKeywords: osteosarcoma; curcumin; apoptosis; ROS; NRF2  \n1. Introduction  \nOsteosarcoma (OS) is a primary bone malignancy (~20% of newly diagnosed bone tumors) with a low incidence (approximately 1–3 cases in one million), and it mostly strikes the adolescent and the senior citizen [1–3] . Although OS is rare, it is aggressive, and pulmonary and skeletal metastases are common in OS patients. Surgical resection combined with chemotherapy is the primary remedy for OS [4] . Extended resection is usually employed to prevent the local recurrence of OS, which may cause severe bone defects. Due to voluminous bone loss, it is highly universal for OS patients to suffer dysfunction, weakening the quality of life. Hence, bone rehabilitation cannot be ignored in comprehensive OS treatment. However, bone rehabilitation is still a massive challenge for OS patients after surgery because of the potential tumor relapse. Clinically, there is high demand for an agent with anti-cancer and pro-osteogenic properties in OS treatment.  \nReactive oxygen species (ROS), the byproduct of normal oxygen metabolism in cells, including peroxides, superoxide, singlet oxygen, etc., are mainly generated in mitochondria [5,6] . They are involved in various physiological activities (stem cell renewal, cell differentiation, proliferation, etc.), while the over-physiologi","cbCaigsKa8dEIHt8","https://ap.wps.com/l/cbCaigsKa8dEIHt8","pdf",4604892,11,"English","# Abstract\n# Introduction\n## Reactive oxygen species (ROS) and cancer\n## NRF2 regulation of ROS\n## Curcumin (CUR) as an NRF2 agonist","[{\"question\":\"Why are extended surgical resections used for osteosarcoma, and what complication can follow?\",\"answer\":\"Extended resections are common to prevent local recurrence, but they can cause critical-size bone defects. These defects may lead to dysfunction and weaken patients’ quality of life.\"},{\"question\":\"What is the conventional explanation for how curcumin affects osteosarcoma development?\",\"answer\":\"Curcumin is considered a natural antioxidant that promotes NRF2 nuclear translocation. NRF2 then activates antioxidase transcription, helping cells circumvent excessive ROS that are harmful.\"},{\"question\":\"What did the in vitro results show regarding curcumin, ROS, DNA damage, and apoptosis in MG-63 cells?\",\"answer\":\"Curcumin at 10 and 20 µM increased intracellular ROS in MG-63 cells, damaged their DNA, and ultimately caused apoptosis, even though NRF2 protein levels and NRF2-regulated antioxidase gene expression were increased.\"}]","Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species | PDF",1790260328,28]