Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growth<i>in vitro</i>and<i>in vivo</i>

Shinoda, Shuhei; Kaino, Seiji; Amano, Shogo; Harima, Hirofumi; Matsumoto, Toshihiko; Fujisawa, Koichi; Takami, Taro; Yamamoto, Naoki; Yamasaki, Takahiro; Sakaida, Isao

doi:10.18632/oncotarget.25421

Cited by 30 publications

(21 citation statements)

References 29 publications

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“…Much is still unknown regarding the mechanism of action of iron chelators. We have investigated the ability of DFX ability to suppress tumour proliferation, and found that it suppresses proliferation in a concentration-dependent manner [10], it improves sensitivity to GEM [11], and that the combination of DFX and sorafenib is better than DFX alone at suppressing liver cancer [12]; we have also examined other secondary effects of iron chelators. Upon conducting a supplementary microarray analysis of the in vivo samples used [10], we observed that the expression of Rho-family genes like Rac1 and Cdc42, involved in cellular movement pathways, was altered in DFX-treated cells, and have begun to consider the possibility that DFX could reduce the metastatic and invasive capabilities of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox

et al. 2020

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Background: Iron is required for cellular metabolism, and rapidly proliferating cancer cells require more of this essential nutrient. Therefore, iron regulation may well represent a new avenue for cancer therapy. We have reported, through in vitro and in vivo research involving pancreatic cancer cell lines, that the internal-use, nextgeneration iron chelator deferasirox (DFX) exhibits concentration-dependent tumour-suppressive effects, among other effects. After performing a microarray analysis on the tumour grafts used in that research, we found that DFX may be able to suppress the cellular movement pathways of pancreatic cancer cells. In this study, we conducted in vitro analyses to evaluate the effects of DFX on the invasive and migratory abilities of pancreatic cancer cells. Methods: We used pancreatic cancer cell lines (BxPC-3, Panc-1, and HPAF II) to examine the efficacy of DFX in preventing invasion in vitro, evaluated using scratch assays and Boyden chamber assays. In an effort to understand the mechanism of action whereby DFX suppresses tumour invasion and migration, we performed G-LISA to examine the activation of Cdc42 and Rac1 which are known for their involvement in cellular movement pathways. Results: In our scratch assays, we observed that DFX-treated cells had significantly reduced invasive ability compared with that of control cells. Similarly, in our Boyden chamber assays, we observed that DFX-treated cells had significantly reduced migratory ability. After analysis of the Rho family of proteins, we observed a significant reduction in the activation of Cdc42 and Rac1 in DFX-treated cells. Conclusions: DFX can suppress the motility of cancer cells by reducing Cdc42 and Rac1 activation. Pancreatic cancers often have metastatic lesions, which means that use of DFX will suppress not only tumour proliferation but also tumour invasion, and we expect that this will lead to improved prognoses.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox

et al. 2020

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“…Moreover, in breast cancer patient-derived xenograft models, it has been reported that tumor recurrences are delayed by the combination without enhancing the side-effects of chemotherapies or impairing systematic iron homeostasis of the mice [182,183]. DFX can also synergistically repress pancreatic cancer cell proliferation with gemcitabine, a standard chemotherapy for pancreatic cancer, in vitro and in vivo [184].…”

Section: Iron Manipulating Strategies In Cancermentioning

confidence: 99%

Iron Metabolism in Cancer

Wang

Ding

et al. 2018

IJMS

216

159

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Demanded as an essential trace element that supports cell growth and basic functions, iron can be harmful and cancerogenic though. By exchanging between its different oxidized forms, iron overload induces free radical formation, lipid peroxidation, DNA, and protein damages, leading to carcinogenesis or ferroptosis. Iron also plays profound roles in modulating tumor microenvironment and metastasis, maintaining genomic stability and controlling epigenetics. in order to meet the high requirement of iron, neoplastic cells have remodeled iron metabolism pathways, including acquisition, storage, and efflux, which makes manipulating iron homeostasis a considerable approach for cancer therapy. Several iron chelators and iron oxide nanoparticles (IONPs) has recently been developed for cancer intervention and presented considerable effects. This review summarizes some latest findings about iron metabolism function and regulation mechanism in cancer and the application of iron chelators and IONPs in cancer diagnosis and therapy.

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“…Chelators are frequently used in combination with other therapies. As an example, DFO was associated with many different chemotherapeutic drugs such as cyclophosphamide, thiotepa, etoposide, carboplatin and cisplatin [121][122][123]. However, some cancers are resistant to Fe-chelators, probably because of their low membrane permeability properties [119].…”

Section: Fe Chelatorsmentioning

confidence: 99%

Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy

Lelièvre

Sancey

Coll

et al. 2020

Preprint

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Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production, or oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of turning these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and /or response to anticancer treatments. Additionally, the iron addiction of cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we selected relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides, we discuss some co-existing discrepant findings. We will also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anti-cancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy will also be reported.

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Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growthin vitroandin vivo

Cited by 30 publications

References 29 publications

RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox

RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox

Iron Metabolism in Cancer

Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy

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