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Drug Res (Stuttg) 2022; 72(04): 203-208
DOI: 10.1055/a-1766-5491
Original Article

Carvacrol Enhance Apoptotic Effect of 5-FU on MCF-7 Cell Line via inhibiting P-glycoprotein: An In-silco and In-vitro Study

Vajihe Ghorbanzadeh
1   Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
,
Karwan Anwar Hassan Aljaf
2   Medical Laboratory Analysis, Cihan University-Sulaimaniya, Slemani, Iraq
,
Hunar Mustafa Wasman
3   Medical Laboratory Science Department, University of Raparin, Kurdistan Region, Iraq
,
Lale Pirzeh
4   Institute for Vascular Signaling, Center for Molecular Medicine, Johann Wolfgang Goethe University Frankfurt, Frankfort am Main, Germany
,
Saleh Azimi
5   Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
,
Hassan Dariushnejad
1   Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
5   Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
› Author Affiliations Funding This study was funded by Deputy of Research and Technology (grant No. 1881), Lorestan University of Medical Sciences, Khorramabad, Iran.
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Abstract

Background P-glycoprotein (P-gp), is an ATP-dependent efflux transporter and overexpressed in cancer cells which is responsible for drug resistance and transportation of anticancer agents out of cells. Hence, P-gp inhibition is a promising way to reverse multi-drug resistance, finding a suitable inhibitor is essential. Carvacrol, an active compound of thyme, has been shown anticancer properties in several types of cancers but the mechanisms underlying this effect remain unclear. Here, we evaluated the inhibitory effects of carvacrol on P-gp by In-silco and in-vitro studies.

Method carvacrol was docked against P-gp via autodock vina software to identify the potential binding of this agent. Verapamil, a well-known P-gp inhibitor, was selected as the control ligands. Cell proliferation and apoptosis were assessed using MTT assay and ELISA cell death assay, respectively.

Results It was observed that carvacrol exhibited appropriate affinity (−7 kcal/mol) to drug binding pocket of P-gp when compared with verapamil that showed binding affinities of −8 kcal/mol. The result of MTT assay showed a dose-dependent inhibitory effect of carvacrol and 5-FU. Data of apoptosis assay showed that combining carvacrol with 5-FU increased apoptotic effect of 5-FU 6.7-Fold rather than the control group. This ability to enhance apoptosis is more than the combination of verapamil and 5-FU (4.26-Fold).

Conclusion These results provide important evidence that carvacrol may be a promising agent able to overcome P-gp-mediated MDR.

Key words

Breast cancer - Carvacrol - Molecular docking - Multi Dug Resistance - P-glycoprotein


Publication History

Received: 03 January 2022

Accepted: 08 February 2022

Article published online:
04 March 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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