The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression

Lei, Guang; Zhang, Yilei; Koppula, Pranavi; Liu, Xiaoguang; Zhang, Jie; Lin, Steven H.; Ajani, Jaffer A.; Xiao, Qin; Liao, Zhongxing; Wang, Hui; Gan, Boyi

doi:10.1038/s41422-019-0263-3

Cited by 684 publications

(489 citation statements)

References 53 publications

Supporting

Mentioning

474

Contrasting

Order By: Relevance

“…IR induces ROS directly by inducing the ACSL4/LPCAT3/ALOX and SLC7A11/GPX4 pathways as an adaptive response. Inactivating SLC7A11 or GPX4 improves the radiosensitivity of cancer cells and xenograft tumors to IR (71). Additionally, ferroptosis has been considered as a direct link to improve tumor control after co-treatments with radiotherapy and CD8+ T cells.…”

Section: Ferroptosis In Cancer Radiotherapymentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

110

View full text Add to dashboard Cite

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.

show abstract

Section: Ferroptosis In Cancer Radiotherapymentioning

confidence: 99%

Ferroptosis in Cancer Treatment: Another Way to Rome

Luo

et al. 2020

Front. Oncol.

110

View full text Add to dashboard Cite

show abstract

“…Ferrroptosis is an iron-dependent form of cell death caused primarily by the peroxidation of phospholipids (PLs) containing polyunsaturated fatty acids (PUFAs) [8]. ACSL4 is a long-chain fatty acidcoenzyme A ligase that is required for PUFA-PLs biosynthesis, which in turn lead to elevated lipid peroxidation and ferroptosis [18,19]. Yuan et al 2016 [6] found that ACSL4 contributes to the accumulation of lipid intermediates during ferroptosis and identi ed ACSL4 as a biomarker and contributor to ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Oleanolic acid inhibits the proliferation of Hela cells in cervical cancer by regulating the ACSL4 ferroptosis signaling pathway

Jiang¹,

Shi

Miao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Cervical cancer continues to be the leading cause of cancer deaths among women worldwide. Oleanolic acid (OA) is a naturally occurring substance found in the leaves, fruits, and rhizomes of plants that has anti-cancer activity. Methods: We used tumor-bearing mice as the animal model and Hela cell as cell models. Western blot was used for detecting the expression of proteins in ferroptosis related proteins acyl-CoA synthase long-chain family member 4 (ACSL4), ferritin heavy chain (FTH1), transferrin receptor (TfR1) and glutathione peroxidase 4 (GPX4) in vivo and in vitro. MTT and EdU was for the detection of the viability of Hela cells. Results: In vivo experiments showed that OA significantly reduced the size and mass of cervical cancer tumors. In vitro experiments showed that OA significantly reduced the viability and proliferation capacity of Hela cells. In both in vivo and in vitro assays, OA increased the level of oxidative stress and Fe2+ content, and increased the expression of ferroptosis related proteins. We found high expression of ACSL4 in both xenograft models and cervical carcinoma cells. Meanwhile, knockdown of ACSL4 expression using shRNA in cervical cancer cells significantly increased cell viability and proliferation. In addition, decreased ROS levels and GPX4 were detected in ACSL4 knockdown cervical cancer cells, suggesting that ACSL4 inhibition may contribute to the reduction of ferroptosis within Hela cells and thus improve Hela cell survival. Conclusion: Promotion of ACSL4 dependent ferroptosis through OA may be an effective approach to treat cervical cancer.

show abstract

“…Employing ferroptosis in combination therapeutics may have the opportunities to enhance the efficacy of existing therapeutic approaches. Ferroptosis is found to enhance the efficacy of immunotherapies [65], chemotherapies [81], and ionization radiations [82][83][84]. DNA damage and ATM/ATR activation have been found to promote ferroptosis [58].…”

Section: Therapeutic Implication and Future Directionmentioning

confidence: 99%

Ferroptosis of epithelial ovarian cancer: genetic determinants and therapeutic potential

Lin

Chi

2020

Oncotarget

View full text Add to dashboard Cite

Epithelial ovarian cancer (OVCA) is the most lethal gynecologic cancer. Current treatment for OVCA involves surgical debulking of the tumors followed by combination chemotherapies. While most patients achieve complete remission, many OVCA will recur and develop chemo-resistance. Whereas recurrent OVCA may be treated by angiogenesis inhibitors, PARP inhibitors, or immunotherapies, the clinical outcomes of recurrence OVCA are still unsatisfactory. One new promising anti-tumor strategy is ferroptosis, a novel form of regulated cell death featured by lipid peroxidation. In this review, we have summarized several recent studies on the ferroptosis of OVCA. Also, we summarize our current understanding of various genetic determinants of ferroptosis and their underlying mechanisms in OVCA. Furthermore, ferroptosis can be combined with other standard cancer therapeutics, which has shown synergistic effects. Therefore, such a combination of therapeutics could lead to new therapeutic strategies to improve the response rate and overcome resistance. By understanding the genetic determinants and underlying mechanisms, ferroptosis may have significant therapeutic potential to improve the clinical outcome of women with OVCA.

show abstract

The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression

Cited by 684 publications

References 53 publications

Ferroptosis in Cancer Treatment: Another Way to Rome

Ferroptosis in Cancer Treatment: Another Way to Rome

Oleanolic acid inhibits the proliferation of Hela cells in cervical cancer by regulating the ACSL4 ferroptosis signaling pathway

Ferroptosis of epithelial ovarian cancer: genetic determinants and therapeutic potential

Contact Info

Product

Resources

About