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Introduction
Reactive oxygen species (ROS) are short-lived, highly electrophilic molecules. They are produced from secondary metabolites generated by a partial reduction of oxygen (1). When intracellular antioxidants are reduced or ROS accumulate excessively, an imbalance in the redox state occurs, which is referred to as oxidative stress. Under such conditions, excessive intracellular accumulation of ROS modifies redox-sensitive amino acid residues in regulatory proteins and alters the actions of proteins and enzymes. Protein kinases, transcription factors and the ubiquitin-proteasome system are vulnerable to excessive accumulation of ROS (2). Of note, when this occurs in tumor cells, it promotes tumor development. Stimulation of signaling pathways by ROS promotes the proliferation, migration and invasion of tumor cells, including in human breast, skin and liver cancers (3). Furthermore, oxidative stress caused by excessive accumulation of ROS can lead to genetic instability. Cell death modalities, such as apoptosis, autophagy, ferroptosis and pyroptosis, act as protective mechanisms to prevent the proliferation of damaged cells (4) and this is also seen in tumor cells. Thus, ROS effects are complex in tumor cells (5,6). Specifically, tumor cells maintain moderate-to-high ROS levels, namely, above the low cytostatic level and below the cytotoxic level, by enhancing their own antioxidant capacity. Therefore, the ROS level in tumor cells is subtoxic, which facilitates tumor cell progression, and ROS act as signaling molecules to increase the proliferation of tumor cells (7–10). However, under further oxidative stress, cancer cells are equally susceptible to excessive ROS (11), and increased ROS unbalance the redox response of cancer cells, ultimately leading to cellular senescence or death (12).
Curcumin is a plant polyphenol in the rhizome of turmeric and was classified as a third-generation cancer chemopreventive agent by the National Cancer Institute (13). Several studies have reported anticancer mechanisms mediated by curcumin through the induction of elevated ROS (14,15). This contradicts the antioxidant properties of curcumin, the potential reasons for which are discussed in the present review. Unfortunately, properties such as poor water solubility and low bioavailability limit the clinical application of curcumin (13). However, the clinical efficacy of curcumin has been enhanced by combining it with drugs, the introduction of nanocarriers and the development of curcumin derivatives, which have brought the clinical application of curcumin closer to reality (16–18). Therefore, the...