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*   Pages 2285 - 2292 ( 8 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

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

Affiliation:

Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran

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