Deferasirox shows inhibition activity against cervical cancer in vitro and in vivo.

Abstract

OBJECTIVE:

Iron depletion may be a novel therapeutic strategy for cancer. This study aimed to assess the inhibition effects of deferasirox (DFX), an oral iron chelator, on cervical cancer.

METHODS:

In this study, we performed immunohistochemical analysis, enzyme-linked immunoassay, cell viability and invasive ability assay, cell cycle and apoptosis analysis, protein expression investigation, molecular mechanism investigation, and in vivo murine xenograft model to evaluate the impact of DFX on cervical cancer.

RESULTS:

The cervical cancer cell lines viability decreased and cell apoptosis was induced after DFX incubation. Additionally, DFX promoted cell cycle arrest by regulating the expression of cell cycle regulators cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) in cervical cancer cell lines. DFX also decreased cell invasion by upregulating the expression of NDRG1 and downregulating c-Myc. The activation of Akt and the MEK/ERK signaling pathway was inhibited by DFX. DFX also significantly suppressed xenograft tumor growth, decreased the levels of ferritin in serum and tumor tissue, reduced iron deposits and reactive oxygen species (ROS) levels in xenografts of DFX-treated group compared with the control group, with no serious side effects.

CONCLUSION:

Present study demonstrated the inhibitory effect of DFX against cervical cancer, and provided a potential therapeutic agent for cervical cancer.

• Authors: Nan Zhou, Yan Cui, Rui Zhu, Yuhuan Kuang, Wenhui Ma, Jianyuan Hou, Yumeng Zhu, Shubo Chen, Xin Xu, Ke Tan, Pengxiu Cao, Xianglin Duan, Yumei Fan
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 166 Issue 1 Pg. 126-137 (07 2022) ISSN: 1095-6859 [Electronic] United States
• PMID: 35688655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Benzoates
• Iron Chelating Agents
• Triazoles
• Iron
• Deferasirox

Topics

• Animals
• Benzoates (pharmacology, therapeutic use)
• Deferasirox (pharmacology)
• Female
• Humans
• Iron
• Iron Chelating Agents (pharmacology, therapeutic use)
• Mice
• Triazoles (pharmacology, therapeutic use)
• Uterine Cervical Neoplasms (drug therapy)