Publication:
Shikonin suppresses lymphangiogenesis via NF-κB/HIF-1α axis inhibition

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Issued Date

2018

Resource Type

Article

File Type

application/pdf

ISSN

9186158

DOI

10.1248/bpb.b18-00329

Other identifier(s)

2-s2.0-85055857122

Rights Holder(s)

Scopus

Bibliographic Citation

Biological and Pharmaceutical Bulletin. Vol 41, No.11 (2018), p.1659-1666

Suggested Citation

Prangsaengtong O., Jantaree P., Lirdprapamongkol K., Svasti J., Koizumi K. Shikonin suppresses lymphangiogenesis via NF-κB/HIF-1α axis inhibition. Biological and Pharmaceutical Bulletin. Vol 41, No.11 (2018), p.1659-1666. doi:10.1248/bpb.b18-00329 Retrieved from: https://hdl.handle.net/20.500.14740/3895

Title

Shikonin suppresses lymphangiogenesis via NF-κB/HIF-1α axis inhibition

Author(s)

Prangsaengtong O.
 Jantaree P.
 Lirdprapamongkol K.
 Svasti J.
 Koizumi K.

Abstract

Lymphangiogenesis, the formation of lymphatic vessels from preexisting ones, promotes cancer growth and metastasis. Finding natural compounds with anti-lymphangiogenic activity will be useful for preventive treatment of lymphatic metastasis. Shikonin, an ingredient of a traditional Japanese and Chinese medicinal herb Lithospermum erythrorhizon, has been widely used in several pharmaceutical and cosmetic preparations, as well as in food colorants. Shikonin has been reported to inhibit lymphangiogenesis in vitro, but the mechanism of inhibition has not been determined. The aim of this study is to investigate the mechanism of anti-lymphangiogenesis of shikonin in primary human lymphatic endothelial cells (HMVEC-dLy). Shikonin, at non-toxic concentrations, significantly inhibited cord formation ability of lymphatic endothelial cells in a dose- and time-dependent manner. Western blotting analysis showed that shikonin decreased nuclear factor-kappaB (NF-κB) activation, as indicated by phosphorylation and nuclear translocation of NF-κB p65, and also reduced both mRNA and protein levels of hypoxia-inducible factor-1 (HIF-1)α. Use of an NF-κB inhibitor (BAY 11-7085) and HIF-1α small interfering RNA (siRNA) transfection revealed that NF-κB activation was upstream of HIF-1α expression, which controls cord formation by HMVEC-dLy. In addition, the reduction of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3) mRNA levels were also found in HMVEC-dLy that treated with shikonin. In conclusion, shikonin inhibits lymphangiogenesis in vitro by interfering the NF-κB/HIF-1α pathway and involves in suppression of VEGF-C and VEGFR-3 mRNA expression. © 2018 The Pharmaceutical Society of Japan

Subject(s)

3 (4 tert butylphenylsulfonyl) 2 propenenitrile
 Hypoxia inducible factor 1alpha
 Immunoglobulin enhancer binding protein
 Messenger RNA
 Shikonin
 Small interfering RNA
 Synaptotagmin I
 Vasculotropin C
 Vasculotropin receptor 3
 Herbaceous agent
 Hypoxia inducible factor 1alpha
 Immunoglobulin enhancer binding protein
 Messenger RNA
 Naphthoquinone
 Shikonin
 Vasculotropin C
 Vasculotropin receptor 3
 Article
 Cancer inhibition
 Concentration (parameters)
 Controlled study
 Endothelium cell
 Genetic transfection
 Human
 Human cell
 In vitro study
 Lymph vessel endothelium
 Lymphangiogenesis
 Nucleocytoplasmic transport
 Protein phosphorylation
 Western blotting
 Chemistry
 Drug effect
 Genetics
 Lithospermum
 Lymph node metastasis
 Lymphangiogenesis
 Metabolism
 Phytotherapy
 Drugs, Chinese Herbal
 Endothelial Cells
 Humans
 Hypoxia-Inducible Factor 1, alpha Subunit
 Lithospermum
 Lymphangiogenesis
 Lymphatic Metastasis
 Naphthoquinones
 NF-kappa B
 Phytotherapy
 RNA, Messenger
 Vascular Endothelial Growth Factor C
 Vascular Endothelial Growth Factor Receptor-3

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URI

https://hdl.handle.net/20.500.14740/3895

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Scopus: Year 1983-2021

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