Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer

Abstract The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknow...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Meng-Chuan Chen, Wen-Lin Hsu, Wen-Liang Chang, Tz-Chong Chou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2996d676c3f4a0e9d68da5105010343
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e2996d676c3f4a0e9d68da5105010343
record_format	dspace
spelling	oai:doaj.org-article:e2996d676c3f4a0e9d68da51050103432021-12-02T12:31:53ZAntiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer10.1038/s41598-017-05512-92045-2322https://doaj.org/article/e2996d676c3f4a0e9d68da51050103432017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05512-9https://doaj.org/toc/2045-2322Abstract The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors. Treatment with AE-AS markedly decreased the protein accumulation and transcriptional activity of HIF-1α, vascular endothelial growth factor (VEGF) expression/secretion, and VEGFR2 phosphorylation in hypoxic human bladder cancer (T24) cells and tumor tissues accompanied by a reduction of tumor growth. Notably, AE-AS-induced HIF-1α protein degradation may, at least partly, attribute to inhibition of WSB-1-dependent pVHL degradation. Moreover, VEGFR2-activated PI3K/AKT/mTOR signaling pathway in hypoxic T24 cells was greatly inhibited by AE-AS. Collectively, AE-AS may be a potential anticancer agent by attenuating cancer angiogenesis via suppression of WSB-1/pVHL/HIF-1α/VEGF/VEGFR2 cascade.Meng-Chuan ChenWen-Lin HsuWen-Liang ChangTz-Chong ChouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Meng-Chuan Chen Wen-Lin Hsu Wen-Liang Chang Tz-Chong Chou Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
description	Abstract The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors. Treatment with AE-AS markedly decreased the protein accumulation and transcriptional activity of HIF-1α, vascular endothelial growth factor (VEGF) expression/secretion, and VEGFR2 phosphorylation in hypoxic human bladder cancer (T24) cells and tumor tissues accompanied by a reduction of tumor growth. Notably, AE-AS-induced HIF-1α protein degradation may, at least partly, attribute to inhibition of WSB-1-dependent pVHL degradation. Moreover, VEGFR2-activated PI3K/AKT/mTOR signaling pathway in hypoxic T24 cells was greatly inhibited by AE-AS. Collectively, AE-AS may be a potential anticancer agent by attenuating cancer angiogenesis via suppression of WSB-1/pVHL/HIF-1α/VEGF/VEGFR2 cascade.
format	article
author	Meng-Chuan Chen Wen-Lin Hsu Wen-Liang Chang Tz-Chong Chou
author_facet	Meng-Chuan Chen Wen-Lin Hsu Wen-Liang Chang Tz-Chong Chou
author_sort	Meng-Chuan Chen
title	Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
title_short	Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
title_full	Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
title_fullStr	Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
title_full_unstemmed	Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer
title_sort	antiangiogenic activity of phthalides-enriched angelica sinensis extract by suppressing wsb-1/pvhl/hif-1α/vegf signaling in bladder cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e2996d676c3f4a0e9d68da5105010343
work_keys_str_mv	AT mengchuanchen antiangiogenicactivityofphthalidesenrichedangelicasinensisextractbysuppressingwsb1pvhlhif1avegfsignalinginbladdercancer AT wenlinhsu antiangiogenicactivityofphthalidesenrichedangelicasinensisextractbysuppressingwsb1pvhlhif1avegfsignalinginbladdercancer AT wenliangchang antiangiogenicactivityofphthalidesenrichedangelicasinensisextractbysuppressingwsb1pvhlhif1avegfsignalinginbladdercancer AT tzchongchou antiangiogenicactivityofphthalidesenrichedangelicasinensisextractbysuppressingwsb1pvhlhif1avegfsignalinginbladdercancer
_version_	1718394249560457216

Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer

Ejemplares similares