Drug Res (Stuttg) 2022; 72(04): 220-225
DOI: 10.1055/a-1775-7908
Original Article

Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells

Narjes Sanapour
1   Department of Clinical Biochemistry, Tabriz University of Medical Sciences, Tabriz, Iran
,
Faezeh Malakoti
1   Department of Clinical Biochemistry, Tabriz University of Medical Sciences, Tabriz, Iran
,
Darioush Shanebandi
2   Molecular Medicine Research Center, Tabriz University of Medical Sciences, Iran
,
Niloufar Targhazeh
2   Molecular Medicine Research Center, Tabriz University of Medical Sciences, Iran
,
Bahman Yousefi
2   Molecular Medicine Research Center, Tabriz University of Medical Sciences, Iran
,
Jafar Soleimanpour
2   Molecular Medicine Research Center, Tabriz University of Medical Sciences, Iran
3   Department of Orthopedics Surgery, Shohada Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
,
Maryam Majidinia
4   Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
› Author Affiliations

Abstract

Background Osteosarcoma (OS) as the most frequent primary bone malignancy in children and adolescents has a short survival rate in advanced stages. Alternative herbal medicines with fewer side effects or the potency to protect common therapy’s side effects can be helpful in combinational therapies. Herein, we aim to explore the effects of Thymoquinone (TQ) combined with Methotrexate (MTX) on Saos-2 cells apoptosis.

Methods The effects of TQ and MTX alone or in combination on Saos-2 cell viability were measured by MTT assay. Real-time PCR was applied for the measurement of Bax, BCL-2, and caspase-9 mRNA expression. Apoptosis evaluation was conducted by flow cytometry.

Results TQ improves the cytotoxic effects of MTX on Saos-2 cells proliferation at lower doses. Indeed, the IC50 of MTX decreased from 26 μM to 15 μM when it combined with TQ. TQ and MTX can induce the expression level of pro-apoptotic factors, Bax and caspase-9 while inhibiting anti-apoptotic protein BCL-2. Moreover, the combination of TQ and MTX potentiates apoptosis to 73%, compared to either TQ (48%) or MTX (53%) treated cells.

Conclusion The co-treatment of TQ and MTX is associated with the up-regulation of apoptotic factors and down-regulation of anti-apoptotic factors, conducting apoptosis aggravation and OS cell death.



Publication History

Received: 05 December 2021

Accepted: 07 February 2022

Article published online:
06 April 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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