The iron chelator desferrioxamine synergizes with chemotherapy for cancer treatment

• Published in: Journal of trace elements in medicine and biology Vol. 56; pp. 131 - 138
• Main Authors: Wang, Lingjuan, Li, Xiaoqing, Mu, Yanxi, Lu, Chang, Tang, Shiqian, Lu, Kun, Qiu, Xiaoming, Wei, Aili, Cheng, Yongjiu, Wei, Wei
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.12.2019
• Subjects: Aldehyde Dehydrogenase - metabolism; Antigens, CD - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer therapy; CDDP; Cell Line, Tumor; Cell Proliferation - drug effects; Cisplatin - pharmacology; Cisplatin - therapeutic use; Deferoxamine - pharmacology; Deferoxamine - therapeutic use; DFO; Disease Progression; Drug Synergism; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Intracellular Space - metabolism; Iron - metabolism; Iron Chelating Agents - pharmacology; Iron Chelating Agents - therapeutic use; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Tumor Suppressor Protein p53 - metabolism; CDDP; DFO; Cancer therapy; Ovarian cancer
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2019.07.008

•Desferrioxamine is associated with depleted the CSCs of ovarian cancer.•Intracellular iron concentration is associated with reduced cisplatin resistance of ovarian cancer.•Desferrioxamine and cisplatin can act as a new effective combination therapy in ovarian cancer. Cisplatin (CDDP) resistance remains a major obstacle for treatment of ovarian cancer. Iron contributes to the growth and reproduction of malignant cells, thus iron chalators can inhibit the growth of tumor cells by depleting the intracellular iron pool. The iron chelator, desferrioxamine (DFO), has performed anticancer in previous study. The aim of our study is to determine the correlation between iron-deprivation and tumor chemosensitivity in ovarian cancer. To investigate the prognostic value of ferritin light (FTL), ferroportin (FPN), hepcidin (HAMP) and divalent metal-ion transporter-1 (DMT1) in ovarian cancer, the Kaplan–Meier analysis and the Gene Expression Profiling Interactive Analysis (GEPIA) were used. The ovarian cancer cell lines (SKOV-3 and OVCAR-3) were exposed to a gradient concentration of DFO (10, 20, 50, 100, 200 μM) and CDDP (1, 5, 10, 50,100 μM) for 24 h. The protein expression of FTL was tested. The expression of cancer stem cell (CSC) markers, including Sox2, Nanog and C-myc, were downregulated with treatment of DFO. Also, the mamosphere formation and the plation of CD44+/high/CD133+/high and Aldehyde dehydrogenase (ALDH)+/high SKOV-3 cells were reduced after treatment for 7d. Furthermore, we detected the expression of p53, BCL-2, BAX, and caspase-8. The survival analysis revealed that high expression of FTL, DMT1, HAMP, showed poor overall survival (OS) in ovarian cancer patients. Our combined data found that DFO could effectively inhibit CSCs, improve the resistance to chemotherapy, and significantly enhanced the efficacy of CDDP therapy in vitro in promoting apoptosis. Besides, targeting molecular targets, including BAX, BCL-2, p53 and caspase-8 could serve as the clinical biomarkers to evaluate the effects of ovarian cancer. It is reasonable to believe that DFO adjuvant therapy in combination with CDDP chemotherapy can promote the improvement of treatment response in ovarian cancer patients. Our research suggests the experimental evidence for DFO and CDDP as a new effective combination therapy to enhance the efficacy of chemical therapy in ovarian cancer.