Abstract
Purpose
Hepatocellular carcinoma (HCC) is the uncontrolled growth of hepatocytes which results in nearly 5 million deaths worldwide. Specific strategies have been developed to treat HCC, including surgery, chemotherapy and radiotherapy. But, the effective disease dealing requires synergistic collaboration with other approaches, which often results in moderate to severe side effects during and after the treatment period. Therefore, the focus is now shifting to explore and retrieve those plant-based products that could be utilized to treat HCC with maximum efficacy without causing any side effects. Strigolactones (SL) are compounds of plant origin derived from Striga lutea responsible for controlling the branching pattern of stem and have reported anti-cancerous activity by promoting apoptosis at micromolar concentrations. However, little work has been done concerning determining the pharmacogenomic effect of strigolactones on HCC.
Methods
Current work focuses on comparing therapeutic efficiencies of SL analogs against core targets of HCC using network pharmacology approach, pharmacokinetics analysis, gene ontogeny, functional enrichment analysis, molecular docking and Molecular Dynamics simulation.
Results
Drug-target prediction and functional enrichment analysis showed that HDAC1 and HDAC2 are the core proteins involved in hepatocellular carcinoma that strigolactone analogs can target. Consequently, results from molecular docking and MD simulation analyses report that among all the SL analogs strigol, epistrigol and nijmegen1 can turn out to be most effective in downregulating the expression of HDAC1, HDAC2 and CYP19A.
Conclusion
Strigol, epistrigol and nijmegen1 could be used as potential inhibitors against HCC and can be further validated through in vitro/in vivo studies.
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Supplementary information or data can be obtained from the author on request.
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Acknowledgements
Authors are grateful to Director, Indian Institute of Information Technology, Allahabad, India for providing facilities for research and to Ministry of Education, India for providing research fellowship. The computational results reported in this work were performed on the Central Computing Facility of IIIT Allahabad.
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AA performed analysis and written manuscript. SP helped in performed analysis and done proofreading, PC and AG performed MD simulations analysis, SS designed this study.
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Amod, A., Pahal, S., Choudhary, P. et al. Network pharmacological evaluation of strigolactones efficacy as potential inhibitors against therapeutic targets of hepatocellular carcinoma. Biotechnol Lett 44, 879–900 (2022). https://doi.org/10.1007/s10529-022-03266-7
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DOI: https://doi.org/10.1007/s10529-022-03266-7