Phytochemicals Targeting Ferroptosis: Therapeutic Opportunities and Prospects for Treating Breast Cancer

Zhao, Xin; Wang, Xueni; Pang, Yuzhou

doi:10.3390/ph15111360

Cited by 6 publications

(6 citation statements)

References 103 publications

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“…Polyphenols are natural products known for a plethora of bioactivities, including their diverse effects on ferroptosis cell death [ 13 , 14 , 15 , 16 , 17 , 49 ]. They have shown significant anticancer activity in vitro, even against an aggressive type of cancer, and their chemopreventive role has been summarized elsewhere [ 50 , 51 ].…”

Section: Biological Aspects Of Ferroptosis Modulatorsmentioning

confidence: 99%

“…Herein, we collect sets of 30 representative inducers ( Table 1 and Table S1 ) and 48 suppressors/inhibitors ( Table 2 and Table S2 ) of ferroptotic cell death with a MW of less than 800 and analyze them in relation to structural, physicochemical/drug-likeness, and biological/pharmacological aspects. Thereafter, the review focuses on describing the biological activities/effects of the subset of (poly)phenolic ferroptosis modulators since, to our knowledge, there has been no such comprehensive review of polyphenols as ferroptosis modulators [ 13 , 14 , 15 , 16 , 17 ]. We focus only on the activities of (poly)phenolic compounds (many of which are already known) in conjunction with their reported (anti)ferroptotic effects.…”

Section: Introductionmentioning

confidence: 99%

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Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products

Stepanić

Kučerová-Chlupáčová

2023

Molecules

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Ferroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties. Ferroptosis modulators are mostly natural products or semisynthetic derivatives. In this review, we focused on the abundant subgroup of polyphenolic modulators, primarily phenylpropanoids. Many natural polyphenolic antioxidants have antiferroptotic activities acting through at least one of the following effects: ROS scavenging and/or iron chelation activities, increased GPX4 and NRF2 expression, and LOX inhibition. Some polyphenols are described as ferroptosis inducers acting through the generation of ROS, intracellular accumulation of iron (II), or the inhibition of GPX4. However, some molecules have a dual mode of action depending on the cell type (cancer versus neural cells) and the (micro)environment. The latter enables their successful use (e.g., apigenin, resveratrol, curcumin, and EGCG) in rationally designed, multifunctional nanoparticles that selectively target cancer cells through ferroptosis induction.

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Section: Biological Aspects Of Ferroptosis Modulatorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products

Stepanić

Kučerová-Chlupáčová

2023

Molecules

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“…This current research aims to further enrich our understanding of the various natural product‐mediated mechanisms regulating ferroptosis and expand our knowledge of the regulatory mechanisms involving ferroptosis‐related signalling pathways and associated metabolic pathways. 289 These signalling pathways hold great promise as potential targets for anti‐breast cancer drugs. Furthermore, there is an urgent need to explore the intricate mechanisms underlying this novel form of cell death in breast cancer, particularly within the context of lipid peroxidation and ferroptosis‐sensitive metabolic pathways.…”

Section: Prospectmentioning

confidence: 99%

“…PROS PEC T A recent study briefly outlined the regulatory effects of phytochemicals on ferroptosis in breast cancer, but the detailed mechanisms of ferroptosis in breast cancer were not extensively explored. This current research aims to further enrich our understanding of the various natural product-mediated mechanisms regulating ferroptosis and expand our knowledge of the regulatory mechanisms involving ferroptosis-related signalling pathways and associated metabolic pathways 289. These signalling pathways hold great promise as potential targets for anti-breast cancer drugs.…”

mentioning

confidence: 99%

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis

Ge,

He,

Zhao

et al. 2023

J Cellular Molecular Medi

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Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis‐inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

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“…Ferroptosis is different from apoptosis or necroptosis in terms of morphology and biochemistry and can be induced via small molecules such as Erastin, sulfasalazine, and sorafenib [4,6]. There has been evidence that ferroptosis has been associated with a wide variety of diseases, including tumors, and is associated with chemoresistance as well as the ability of immunotherapy to inhibit tumor growth, indicating that it may be a promising treatment strategy for CRC [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

SPINK4 promotes colorectal cancer cell proliferation and inhibits ferroptosis

Yin

et al. 2023

BMC Gastroenterol

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Background Little is known about the role of serine peptidase inhibitor Kazal type 4 (SPINK4) in colorectal cancer (CRC) and ferroptosis. Therefore, this study aimed to determine the effect of SPINK4 on CRC pathogenesis and ferroptosis. Methods SPINK4 expression was analyzed in public datasets and examined using immunohistochemistry. The biological function of SPINK4 in CRC cell lines and its effect on ferroptosis were tested. An immunofluorescence assay was performed to determine the location of SPINK4 in cells, and mouse models were established to determine the effects of SPINK4 in vivo. Results CRC datasets and clinical samples analysis revealed that SPINK4 mRNA and protein levels were significantly reduced in CRC tissues compared to control tissues (P < 0.05). Two CRC cell lines (HCT116 and LoVo) were selected, and the in vitro and in vivo experiments showed that overexpression of SPINK4 greatly promotes the proliferation and metastasis of CRC cells and tumor growth (P < 0.05). The immunofluorescence assay indicated that SPINK4 is mainly located in the nucleoplasm and nucleus of CRC cells. Furthermore, SPINK4 expression was reduced after cell ferroptosis induced by Erastin, and overexpression of SPINK4 greatly inhibited ferroptosis in CRC cells. The results of mouse model further demonstrated that SPINK4 overexpression inhibited CRC cell ferroptosis and facilitated tumor growth. Conclusions SPINK4 was decreased in CRC tissues and promoted cell proliferation and metastasis; overexpression of SPINK4 inhibited CRC cell ferroptosis.

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Phytochemicals Targeting Ferroptosis: Therapeutic Opportunities and Prospects for Treating Breast Cancer

Cited by 6 publications

References 103 publications

Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products

Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis

SPINK4 promotes colorectal cancer cell proliferation and inhibits ferroptosis

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