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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

A Ferrocene Derivative Reduces Cisplatin Resistance in Breast Cancer Cells through Suppression of MDR-1 Expression and Modulation of JAK2/STAT3 Signaling Pathway

Author(s): Shokoofe Noori, Mitra Nourbakhsh, Shabnam Farzaneh and Afshin Zarghi*

Volume 20, Issue 18, 2020

Page: [2285 - 2292] Pages: 8

DOI: 10.2174/1871520620666200807103903

Price: $65

Abstract

Background: Breast cancer is the most common kind of cancer among women in the world. Despite major cancer therapy successes in recent years, cancer cells usually develop mechanisms to survive chemotherapy- induced cell death. Therefore, new strategies are needed to reverse cancer chemoresistance.

Objective: The aim of this study was to investigate the effect of a recently-synthesized ferrocene derivative named 1-ferrocenyl-3-(4-methylsulfonylphenyl)propen-1-one (FMSP) on cisplatin resistance in MCF-7 cells, focusing on its inhibitory effects on Multi-Drug Resistance-1 (MDR-1) and inflammatory-related STAT3 pathway.

Methods: Cisplatin-resistant MCF-7 cells were developed and the effect of cisplatin and FMSP on cell viability was examined by MTT assay. RT-PCR and Western blotting analyses were performed to assess the gene and protein expression of MDR-1 as well as phosphorylation of JAK2 and STAT3.

Results: Overexpression of MDR1 as well as a marked increase in the level of phosphorylated STAT3 was observed in cisplatin-resistant MCF-7 (MCF-7R) cells. FMSP successfully reduced the MCF-7R cell viability and reversed both MDR1 expression and STAT3 phosphorylation status through which sensitivity of MCF-7R cells to cisplatin treatment was regained.

Conclusion: Our results indicated that FMSP may be considered as a promising therapeutic agent for the prevention and management of chemoresistance in breast cancer cells.

Keywords: Breast cancer, ferrocene, cisplatin, JAK2, STAT3, MDR-1, chemoresistance.

Graphical Abstract
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