Diterpenoids from Scutellaria barbata induce tumour-selective cytotoxicity by taking the brakes off apoptosis

Tomlinson, Matthew L., Zhao, Man, Barclay, Elaine J., Li, Jie, Li, Haixiu, Felix, Juri, Hill, Lionel, Saalbach, Gerhard, Rejzek, Martin, Yang, Dongfeng, Zhao, Qing, Kroon, Paul, Wang, Wei, Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370, Howes, Melanie-Jayne R., Tatsis, Evangelos C. and Martin, Cathie (2022) Diterpenoids from Scutellaria barbata induce tumour-selective cytotoxicity by taking the brakes off apoptosis. Medicinal Plant Biology, 1. ISSN 0000-0000

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Abstract

Medicinal plants are an excellent source of structurally diverse, bio-active compounds with potential in the fight against cancer. One of the most promising is Scutellaria barbata, prescribed traditionally for the treatment of cancers. Scutebarbatine A is the major diterpenoid, produced in specialized large, peltate trichomes on leaves of S. barbata. It induces dose-dependent apoptosis, specifically in cancer cells. The major class of proteins down-regulated are pro-survival proteins, the Inhibitors of Apoptosis (IAPs), and IAP regulating proteins. We propose that scutebarbatine A works by releasing the molecular brakes (the IAPs) on apoptosis in cell death-evading cancer cells. Comparison between the cytotoxicity of methanolic extracts of S. barbata leaves and decoctions (Ban Zhi Lian) prepared traditionally, showed substantially different chemical compositions and differential induction of apoptosis. Analyses suggest polyvalency between the constituents in both extracts, and ways to produce enhanced chemopreventive preparations for the treatment of cancer.

Item Type: Article
Additional Information: ACKNOWLEDGMENTS: The authors acknowledge the Royal Society for a Newton Advanced Fellowship awarded to ECT (NAF\R2\192001) and CEPAMS Funding (Project CPM19) for support of a collaboration project 'Scutellaria Anticancer Metabolites' for E.C.T., C.M., M-J.R.H., J.F. and Q.Z. C.M., M.T., E.B., M.R., G.S., L.H.. and J.L. were also supported by the Institute Strategic Programme ‘Molecules from Nature’ (BB/ P012523/1) from the UK Biotechnology and Biological Sciences Research Council. MZ was supported by a CSC visiting scholarship and by the Natural Science Foundation of Zhejiang Province, China (LY21H280009). They thank CAS for the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB27020204) and for International Partnership Program of CAS (153D31KYSB20160074); gratefully acknowledge the Ministry of Science and Technology for Foreign Expert Project 2019 (G20190113016), the Science and Technology Commission of Shanghai Municipality for Shanghai Talent Recruitment Program 2018 and funds from National Key Laboratory of Plant Molecular Genetics and Shanghai Institute of Plant Physiology and Ecology to ECT for support of this project.
Uncontrolled Keywords: diterpenoids,cancer,apoptosis,scutellaria barbata,plant,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 05 Jul 2022 10:30
Last Modified: 13 Nov 2023 17:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/85947
DOI: 10.48130/MPB-2022-0003

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