Elucidation of natural compounds Gallic acid and Shikonin for the treatment of HNSC cancer by targeting immune suppressor and tumour progressor genes


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Print ISSN : 0970-4078.
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Doi: 10.1007/s42535-022-00363-w
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Keywords: Head and neck squamous cell carcinoma (HNSC), Immunomodulation, Natural compounds, Gallic acid, Shikonin


Head and Neck Squamous cell carcinoma is a leading cancer in males, especially in India. Progression of tumour growth in conjunction with immune suppression is the major cause that leads to HNSC cancer. Synthetic drugs targeting tumour cells often trigger tumour cells to acquire resistance against them. Immunotherapy also has its side effects and does not provide an adequate response in all patients, and its inherent variability in patient response often makes them prohibitive. Hence, a concomitant targeting of tumour cells and modulation of immune cell function may be particularly beneficial mechanism for cancer treatment. In the present study, we tried to identify natural compounds that could help in tumour suppression as well as functional immune modulation. The HNSC-associated genes that played role in both tumour growth and immune suppression were identified by enrichment analysis followed by gene expression analysis. 10 such genes were shortlisted, namely Foxp3, CD274, IDO1, IL-10, SOCS1, PRKDC, AXL, CDK6, TGFB1, FADD. CD274 and IDO1 which were found to have the highest degree of interaction based on their network of interactions. Gallic acid and Shikonin were found as the natural compounds that efficiently targeted CD274 and IDO1 respectively. Gallic acid is extracted from leaves of bearberry also found, in pomegranate root bark, gallnuts, witch hazel, both in free-state and as also a part of the tannin molecule, whereas Shikonin is found in the extracts of dried roots of the plant Lithospermum erythrorhizon. Studies have demonstrated that both Shikonin and Gallic acid exhibits anti-cancer properties. Expression data analysis of HNSC cancer exhibited 1745 differentially expressed genes. Gallic acid treatment resulted in the downregulation of 120 genes and upregulation of 35 genes while Shikonin treatment resulted in the downregulation of 660 genes and upregulation of 38 genes that are consequential in a positive impact of cancer regression. Thus, combination of these two compounds could be potentially beneficial in effective combinatorial therapy for HNSC.

Head and neck squamous cell carcinoma (HNSC), Immunomodulation, Natural compounds, Gallic acid, Shikonin

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Author Information

Kumar Sunil
Department of Biotechnology, Delhi Technological University, Delhi, India

Das Asmita
Department of Biotechnology, Delhi Technological University, Delhi, India