Synergistic Effects of Ethanol Extract of Allium sativum (Garlic) with
DAPT and ATRA on Notch Signaling Targeted Molecular Action on Lung
Cancer Cell line (A549)

Ragavi      Ravichandran; D.   David   Wilson; S.      Viswanathan; Siddikuzzaman; Lucia      Bonati; Selvamani      Rajendran; V.   Berlin   Grace

doi:10.2174/1570180820666230831095954

Abstract

Background: The activated oncogenic Notch signalling is an emerging target to treat cancer progression and recurrence. Synthetic inhibitors of Notch receptors are in pre-clinical studies. However, the overexpression of Notch signalling molecules at the gene level needs to be regulated to control cancer progression.

Objective: We propose that this can be achieved by gene-regulatory drugs in combination with natural phytochemical compounds.

Methods: The ethanol extract of Allium sativum alone and in combination with DAPT and ATRA were evaluated for cytotoxicity on A549 cells by MTT and Trypan blue assays. Their effects on Notch 1, Hes 1 and p53 gene expressions were studied by RT-PCR and qPCR. Their inhibition on metastatic invasion of A549 cells was analyzed by in vitro wound scratch assay. The phytochemicals of the extract were identified by GC-MS analysis.

Results: Many organosulfur compounds having anti-cancer potency were identified in GC-MS. The combination treatment with 50μg (IC50) of garlic extract exhibited a highly significant (P≤0.01) synergistic inhibitory effect on A549 cell growth and migration. It has also significantly reduced the expression of Notch 1 and Hes 1 oncogenes and enhanced p53 gene expression, compared with the individual treatments. This indicates the synergistic action of the extract on the downregulation of Notch signalling at the mRNA level.

Conclusion: Our study results imply that the combination therapies have potent molecular treatment action via down-regulating Notch signaling target genes and upregulating p53 gene expression as an underlying mechanism of inhibitory action on A549 lung cancer cells.

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DOI https://dx.doi.org/10.2174/1570180820666230831095954	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

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