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

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.

• Authors: Shokoofe Noori, Mitra Nourbakhsh, Shabnam Farzaneh, Afshin Zarghi
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 20 Issue 18 Pg. 2285-2292 ( 2020) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 32767949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Antineoplastic Agents
• Ferrous Compounds
• Metallocenes
• STAT3 Transcription Factor
• STAT3 protein, human
• JAK2 protein, human
• Janus Kinase 2
• Cisplatin
• ferrocene

Topics

• ATP Binding Cassette Transporter, Subfamily B (antagonists & inhibitors, genetics, metabolism)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Ferrous Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Metallocenes (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Phosphorylation (drug effects)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Structure-Activity Relationship