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悖论:天然抗氧化剂姜黄素通过过量的活性氧抑制骨肉瘤细胞。

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species.

机构信息

Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, 1081 LA Amsterdam, The Netherlands.

出版信息

Int J Mol Sci. 2023 Jul 26;24(15):11975. doi: 10.3390/ijms241511975.

DOI:10.3390/ijms241511975
PMID:37569346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10418684/
Abstract

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 in line 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 μM 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.

摘要

骨肉瘤(OS)是一种罕见的侵袭性肿瘤。广泛的手术切除是 OS 的主要治疗方法,但可能导致临界大小的骨缺损。这些骨缺损导致功能障碍,削弱了患者术后的生活质量。因此,理想的骨肉瘤治疗药物应同时具有抗癌和骨修复能力。姜黄素(CUR)已被报道用于骨肉瘤治疗和骨再生。然而,CUR 如何抑制 OS 发展尚不清楚。传统上,CUR 被认为是一种天然抗氧化剂,符合其促进核转录因子红细胞生成素 2(NRF2)核易位的能力。核易位后,NRF2 可以激活一些抗氧化酶的转录,从而避免对细胞有害的过量活性氧(ROS)。有趣的是,这项研究表明,在体外,10 和 20 μM CUR 增加了 MG-63 细胞内的 ROS,损伤了细胞的 DNA,最终导致 MG-63 细胞凋亡,尽管在这两组细胞中都发现了 NRF2 蛋白水平的增加和 NRF2 调节的抗氧化酶基因的表达。

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