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Review
. 2024 Sep 9;20(12):4838-4852.
doi: 10.7150/ijbs.90798. eCollection 2024.

Potential Roles and Mechanisms of Curcumin and its Derivatives in the Regulation of Ferroptosis

Yuan Zhang  1 , Chenghao Yu  1 , Cheng Peng  1 , Fu Peng  2
Affiliations
Review

Potential Roles and Mechanisms of Curcumin and its Derivatives in the Regulation of Ferroptosis

Yuan Zhang et al. Int J Biol Sci. .

Abstract

Ferroptosis is a recently discovered iron-dependent mode of oxidatively regulated cell death. It is not only associated with a wide range of diseases, but it is also a key component of many signaling pathways. In general, ferroptosis is a double-edged sword. On one hand, it induces nonapoptotic destruction of cancer cells, but on the other, it may lead to organ damage. Therefore, ferroptosis can be drug-targeted as a novel means of therapy. The properties of curcumin have been known for many years. It has a positive impact on the treatment of diseases such as cancer and inflammation. In this review, we focus on the regulation of ferroptosis by curcumin and its derivatives and review the main mechanisms by which curcumin affects ferroptosis. In conclusion, curcumin is a ferroptosis inducer with excellent anticancer efficacy, although it also exhibits organ protective and reparative effects by acting as a ferroptosis inhibitor. The differential regulation of ferroptosis by curcumin may be related to dose and cell type.

Keywords: Anticancer effect; Curcumin; Ferroptosis; Iron; Organ protective effect; Oxidation.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
The chemical structures of curcumin and some of its derivatives (drawing by InDraw).
Figure 2
Figure 2
The sources and biological activities of curcumin.
Figure 3
Figure 3
Curcumin and its derivatives exert antitumor effects by modulating the ferroptosis pathway.
Figure 4
Figure 4
Regulatory mechanisms of curcumin on oxidative stress. Curcumin exerts antioxidant properties by activating both Nrf2-related pathways and the antioxidant system.
Figure 5
Figure 5
Multifaceted roles of curcumin and its derivatives in ferroptosis as the antiferroptosis or pro-ferroptosis agent.
Figure 6
Figure 6
Generation and regulation of cellular ROS. Healthy cells have developed adequate adaptations to overcome the damaging effects of ROS. Balanced generation of ROS, sufficient antioxidant activity and scavenging by macrophages result in low concentrations of ROS. Tumorigenic events including oncogene activation, macrophage infiltration or hypoxia/reoxygenation processes in tissues yield high ROS concentrations. Curcumin-generated ROS become the last straw.
See this image and copyright information in PMC

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