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Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1.

Publication ,  Journal Article
Tong, X; Mirzoeva, S; Veliceasa, D; Bridgeman, BB; Fitchev, P; Cornwell, ML; Crawford, SE; Pelling, JC; Volpert, OV
Published in: Oncotarget
November 30, 2014

Plant flavonoid apigenin prevents and inhibits UVB-induced carcinogenesis in the skin and has strong anti-proliferative and anti-angiogenic properties. Here we identify mechanisms, by which apigenin controls these oncogenic events. We show that apigenin acts, at least in part, via endogenous angiogenesis inhibitor, thrombospondin-1 (TSP1). TSP1 expression by the epidermal keratinocytes is potently inhibited by UVB. It inhibits cutaneous angiogenesis and UVB-induced carcinogenesis. We show that apigenin restores TSP1 in epidermal keratinocytes subjected to UVB and normalizes proliferation and angiogenesis in UVB-exposed skin. Importantly, reconstituting TSP1 anti-angiogenic function in UVB-irradiated skin with a short bioactive peptide mimetic representing exclusively its anti-angiogenic domain reproduced the anti-proliferative and anti-angiogenic effects of apigenin. Cox-2 and HIF-1α are important mediators of angiogenesis. Both apigenin and TSP1 peptide mimetic attenuated their induction by UVB. Finally we identified the molecular mechanism, whereby apigenin did not affect TSP1 mRNA, but increased de novo protein synthesis. Knockdown studies implicated the RNA-binding protein HuR, which controls mRNA stability and translation. Apigenin increased HuR cytoplasmic localization and physical association with TSP1 mRNA causing de novo TSP1 synthesis. HuR cytoplasmic localization was, in turn, dependent on CHK2 kinase. Together, our data provide a new mechanism, by which apigenin controls UVB-induced carcinogenesis.

Duke Scholars

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 30, 2014

Volume

5

Issue

22

Start / End Page

11413 / 11427

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Thrombospondin 1
  • Skin Neoplasms
  • Skin
  • Neovascularization, Pathologic
  • Neoplasms, Radiation-Induced
  • Mice, Inbred BALB C
  • Mice, Hairless
  • Mice
  • Keratinocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tong, X., Mirzoeva, S., Veliceasa, D., Bridgeman, B. B., Fitchev, P., Cornwell, M. L., … Volpert, O. V. (2014). Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1. Oncotarget, 5(22), 11413–11427. https://doi.org/10.18632/oncotarget.2551
Tong, Xin, Salida Mirzoeva, Dorina Veliceasa, Bryan B. Bridgeman, Philip Fitchev, Mona L. Cornwell, Susan E. Crawford, Jill C. Pelling, and Olga V. Volpert. “Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1.Oncotarget 5, no. 22 (November 30, 2014): 11413–27. https://doi.org/10.18632/oncotarget.2551.
Tong X, Mirzoeva S, Veliceasa D, Bridgeman BB, Fitchev P, Cornwell ML, et al. Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1. Oncotarget. 2014 Nov 30;5(22):11413–27.
Tong, Xin, et al. “Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1.Oncotarget, vol. 5, no. 22, Nov. 2014, pp. 11413–27. Pubmed, doi:10.18632/oncotarget.2551.
Tong X, Mirzoeva S, Veliceasa D, Bridgeman BB, Fitchev P, Cornwell ML, Crawford SE, Pelling JC, Volpert OV. Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1. Oncotarget. 2014 Nov 30;5(22):11413–11427.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 30, 2014

Volume

5

Issue

22

Start / End Page

11413 / 11427

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Thrombospondin 1
  • Skin Neoplasms
  • Skin
  • Neovascularization, Pathologic
  • Neoplasms, Radiation-Induced
  • Mice, Inbred BALB C
  • Mice, Hairless
  • Mice
  • Keratinocytes