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

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.

A nanocarrier system based on CQDs for efficient mitoxantrone drug delivery

“…8 ), where Reactive oxygen species generation can disrupt the process of cell [ 29 ]. Moreover, in a previous study, it was reported that curcumin acts as a potent antioxidant agent [ 30 ], and based on the studies performed by Hashemi et al , curcumin loaded in PLGA nanoparticles improved anticancer efficiency of MTX on MCF-7 cells similar to this study's CQD-MTX complex results [ 31 ].…”

Cytotoxicity Enhancement in Osteosarcoma with Multifunctional I-131 Radiotherapeutic Nanoparticles: In Vitro Three-Dimensional Spheroid Model and Release Kinetics Modeling

“…Cancer pathogenesis, chemoresistance, and radioresistance are all influenced by ROS dysregulation. Research by Xu et al verified that curcumin increased the level of ROS in MG-63 cells, stimulating apoptosis [75]. In particular, WNT/β-catenin promotes cell invasion and migration in osteosarcoma, and WNT influences osteosarcoma chemotherapy resistance to cisplatin, doxorubicin, and methotrexate [76].…”

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

“…Curcumin—This polyphenol derived from the turmeric rhizome of Curcuma longa L. is extensively described as an antitumor agent capable of constraining NF-κB pathway activation by interfering with IKK and blocking IκBα and p65 phosphorylation [ 305 ]. The literature reports numerous curcumin antiproliferative and antimigratory effects on OS with modulation of p21, Bax, Bcl-xl, Bcl2, caspase-3, PARP cleavage, cyclin D1, MMP-2, and MMP-9 expression [ 306 , 307 , 308 , 309 , 310 , 311 ].…”