Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Zhou, Haihong; Xu, Chen; Cai, Luya; Nan, X.; Chen, Jiahua; Chen, Xiuxiu; Yang, Yang; Xing, Zihao; Wei, Meng-Ning; Yao, Li; Wang, Sheng-Te; Liu, Kun; Shi, Zhi; Yan, Xiaojian

doi:10.3389/fonc.2019.01398

Cited by 105 publications

(76 citation statements)

References 40 publications

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“…Sorafenib is a multikinase inhibitor approved for the treatment of advanced cancer (e.g., hepatocellular carcinoma) [ 166 ], and it can be used as an agonist of ferroptosis for its inhibitory effect on system xc- [ 167 ]. More importantly, erastin, a more potent inhibitor of system xc-, has been shown to improve the anticancer activity of traditional chemotherapy drugs (e.g., docetaxel, cisplatin, and temozolomide) in several cancer cells [ 168 – 170 ]. Besides its promising role for cancer therapy, ferroptosis is also implicated in multiple forms of tissue damage, including ischemia/reperfusion injury [ 171 ], traumatic injury [ 172 ], and neurodegeneration [ 173 , 174 ].…”

Section: Regulation Of Iron Metabolism For Antitumor Immunitymentioning

confidence: 99%

Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment

Shen

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Leukocytes, including macrophages and T cells, represent key players in the human immune system, which plays a considerable role in the development and progression of tumors by immune surveillance or immune escape. Boosting the recruitment of leukocytes into the tumor microenvironment and promoting their antitumor responses have been hot areas of research in recent years. Although immunotherapy has manifested a certain level of success in some malignancies, the overall effectiveness is far from satisfactory. Iron is an essential trace element required in multiple, normal cellular processes, such as DNA synthesis and repair, cellular respiration, metabolism, and signaling, while dysregulated iron metabolism has been declared one of the metabolic hallmarks of malignant cancer cells. Furthermore, iron is implicated in the modulation of innate and adaptive immune responses, and elucidating the targeted regulation of iron metabolism may have the potential to benefit antitumor immunity and cancer treatment. In the present review, we briefly summarize the roles of leukocytes and iron metabolism in tumorigenesis, as well as their crosstalk in the tumor microenvironment. The combination of immunotherapy with targeted regulation of iron and iron-dependent regulated cell death (ferroptosis) may be a focus of future research.

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Section: Regulation Of Iron Metabolism For Antitumor Immunitymentioning

confidence: 99%

Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment

Shen

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Similarly, overexpression of ABCB1 (P-glycoprotein/MDR1) in ovarian cancers usually leads to chemo-resistance via intracellular drug export (104,105). Erastin can conspicuously reverse the ABCB1-mediated DTXL resistance by limiting the drug efflux activity of ABCB1 (80).…”

Section: Ferroptosis: a Sword To Reverse The Acquired Drug Resistancementioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

124

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Ferroptosis is a newly described type of programmed cell death and intensively related to both maintaining homeostasis and the development of diseases, especially cancers. Inducing ferroptosis leads to mitochondrial dysfunction and toxic lipid peroxidation in cells, which plays a pivotal role in suppressing cancer growth and progression. Here, we reviewed the existing studies about the molecular mechanisms of ferroptosis involved in different antitumor treatments, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy. We focused in particular on the distinct combinatorial therapeutic effects such as the synergistic sensitization effect and the drug-resistance reversal achieved when using ferroptosis inducers with conventional cancer therapy. Finally, we discussed the challenges and opportunities in clinical applications of ferroptosis. The application of nanotechnolgy and other novel technologies may provide a new direction in ferroptosis-driven cancer therapies.

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“…A recent study showed that Erastin can reverse the resistance of ovarian cancer cells to docetaxel by inhibiting the pump activity of ABCB1. The combined use of Erastin and docetaxel provides a new option for the treatment of ovarian cancer resistance (Zhou et al, 2019).…”

Section: Ovarian Carcinomamentioning

confidence: 99%

The Mechanism of Ferroptosis and Applications in Tumor Treatment

et al. 2020

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Iron-dependent ferroptosis is a new form of cell death in recent years, which is driven by lipid peroxidation. The lethal lipid accumulation caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of the ferroptosis process. In recent years, with the in-depth study of ferroptosis, various types of diseases have been reported to be related to ferroptosis. In other words, ferroptosis, which has attracted widespread attention in the fields of biochemistry, oncology, and especially materials science, can undoubtedly provide a new way for patients. This review introduces the relevant mechanisms of ferroptosis, the relationship between ferroptosis and various cancers, as well as the application of ferroptosis in tumor treatment. We also sorted out the genes and drugs that regulate ferroptosis. Moreover, small molecule compound-induced ferroptosis has a strong inhibitory effect on tumor growth in a drugresistant environment, which can enhance the sensitivity of chemotherapeutic drugs, suggesting that ferroptosis is very important in the treatment of tumor drug resistance, but the details are still unclear. How to use ferroptosis to fight cancer, and how to prevent drug-resistant tumor cells have become the focus and direction of research. At the end of the article, some existing problems related to ferroptosis are summarized for future research.

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Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Cited by 105 publications

References 40 publications

Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment

Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment

Ferroptosis in Cancer Treatment: Another Way to Rome

The Mechanism of Ferroptosis and Applications in Tumor Treatment

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