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.
Keywords
Chemotherapy - Combinational therapy - Polyphenol - Black seed (Nigella sativa) - Bone malignancy
