KMID : 0043320200430060655
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Archives of Pharmacal Research 2020 Volume.43 No. 6 p.655 ~ p.665
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Indirubin-3-monoxime and thymoquinone exhibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer
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Dera Ayed A.
Rajagopalan Prasanna Al Fayi Majed Ahmed Irfan Chandramoorthy Harish C.
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Abstract
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In this study, we report the combination of indirubin-3-monoxime (I3M) and thymoquinone (Tq) to have excellent therapeutic efficacy in models of Lung cancer (LC). Preliminary screening was done with A549 cells. Cell cycle, apoptosis and NF¥êB phosphorylation were determined by flow cytometry, while apoptotic proteins, Akt and mTOR were assessed by western blotting. Mouse xenograft model was used to assess the therapeutic efficacy in-vivo. Synergistic reduction in cell viability was observed with I3M?+?Tq combinations, which were non-toxic to normal HFL-1 cells. Cell cycle analysis indicated G1 phase reduction with subsequent accumulation of sub G0 contents. Annexin V assay revealed higher apoptotic cells with combinations compared to individual treatments with a decrease in Bcl-2/Bax ratio. The combinations exhibited anti-metastasis activity in cell migration in the scratch, scatter and tumour cell migration assays and effectively reduced the tumour growth in mouse xenograft model. Expression levels of p-AKT, p-mTOR, Caspase-3, p-53 and NF¥êB were significantly reduced in the combination treated mice compared to individual treatments. Results of current study demonstrate clear efficacy of I3M?+?Tq combinations in LC models mediated by suppressing Akt/mTOR/NF¥êB signalling. Further research is recommended to transform these findings into novel therapeutic combinations against LC.
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KEYWORD
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A549, Akt, Apoptosis, Indirubin, Lung cancer, mTOR, Nf¥êb, Synergism, Thymoquinone
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