Crocin Increases Gastric Cancer Cells' Sensitivity to Doxorubicin.

Seyedeh Mahya Shariat Razavi,Reyhaneh Mahmoudzadeh Vaziri,Fatemeh Kalalinia,Sepideh Arabzadeh,Gholamreza Karimi,Javad Behravan,Vahideh Keyvani

doi:10.31557/apjcp.2020.21.7.1959

Abstract

Background:Crocin is one of the substantial constituents of saffron extract. It has multiple clinical effects including anti-cancer effects. The development of the multidrug resistance (MDR) phenotype is one of the principal causes of cancer chemotherapy failure. The multidrug resistance protein 1 (MDR1) is one of the MDR-related protein and is often overexpressed in different cancers. In the present study, we aimed to evaluate the influence of crocin on the expression and function of MDR1 protein in EPG85-257 and EPG85-257RDB gastric cancer cell lines. Methods:The cytotoxicity effect of crocin was evaluated by the MTT assay. The impacts of crocin on the expression and function of MDR1 were assessed by Real-time RT-PCR and MTT assay, respectively. Results:The results demonstrated that crocin decreased cell viability in a dose-dependent manner with higher intensity on the EPG85-257 than the EPG85-257RDB cells. Crocin did not make any significant changes in the MDR1 gene expression level in EPG85-257 and EPG85-257RDB cell lines. In contrast, crocin increased doxorubicin cytotoxicity in drug-resistant cells, which might be induced by reduced MDR1 activity. Conclusion:In summary, although crocin did not affect mRNA expression of MDR1, results of MTT assay suggest that it might inhibit the MDR1 function.

Highlights

Nowadays, cancer is the second most important cause of mortality and morbidity worldwide
One of the main molecular mechanisms involved in multidrug resistance is an enhanced efflux of the drugs by ATP-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MDR1), that are expressed on the surface of the cells and pump chemotherapy drugs out of the cell
We evaluated the effects of crocin on the expression level and function of MDR1 in the human gastric cancer cell line EPG85-257 and its drug-resistant derivative cell line (EPG85-257RDB)

Summary

Introduction

Cancer is the second most important cause of mortality and morbidity worldwide. In MDR phenomena, cancer cells show resistance to different drugs with different functions and structures that are frequently used in chemotherapy. ATP-binding cassette (ABC) transporters are the main factors that play a role in MDR phenomena through drug efflux. They are transmembrane proteins that pump several substances, including cytotoxic reagents, out of the cell membrane (Samuel et al, 2017). The development of the multidrug resistance (MDR) phenotype is one of the principal causes of cancer chemotherapy failure. We aimed to evaluate the influence of crocin on the expression and function of MDR1 protein in EPG85-257 and EPG85-257RDB gastric cancer cell lines. Conclusion: In summary, crocin did not affect mRNA expression of MDR1, results of MTT assay suggest that it might inhibit the MDR1 function

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