Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery.

Qian, C; Zhou, Y; Zhang, T; Dong, G; Song, M; Tang, Y; Wei, Z; Yu, S; Shen, Q; Chen, W; Choi, JP; Yan, J; Zhong, C; Wan, L; Li, J; Wang, A; Lu, Y; Zhao, Y

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery.

Qian, C Zhou, Y Zhang, T Dong, G Song, M Tang, Y Wei, Z Yu, S Shen, Q Chen, W Choi, JP Yan, J Zhong, C Wan, L Li, J Wang, A Lu, Y Zhao, Y

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Acta Pharm Sin B, 2024, 14, (5), pp. 2077-2096
Issue Date:: 2024-05

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Field	Value	Language
dc.contributor.author	Qian, C
dc.contributor.author	Zhou, Y
dc.contributor.author	Zhang, T
dc.contributor.author	Dong, G
dc.contributor.author	Song, M
dc.contributor.author	Tang, Y
dc.contributor.author	Wei, Z
dc.contributor.author	Yu, S
dc.contributor.author	Shen, Q
dc.contributor.author	Chen, W
dc.contributor.author	Choi, JP
dc.contributor.author	Yan, J
dc.contributor.author	Zhong, C
dc.contributor.author	Wan, L
dc.contributor.author	Li, J
dc.contributor.author	Wang, A
dc.contributor.author	Lu, Y
dc.contributor.author	Zhao, Y
dc.date.accessioned	2024-08-06T01:13:26Z
dc.date.available	2024-02-02
dc.date.available	2024-08-06T01:13:26Z
dc.date.issued	2024-05
dc.identifier.citation	Acta Pharm Sin B, 2024, 14, (5), pp. 2077-2096
dc.identifier.issn	2211-3835
dc.identifier.issn	2211-3843
dc.identifier.uri	http://hdl.handle.net/10453/180021
dc.description.abstract	Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Acta Pharm Sin B
dc.relation.isbasedon	10.1016/j.apsb.2024.02.003
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.title	Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	Netherlands
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2024-08-06T01:13:17Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	14
utslib.citation.issue	5

Abstract:

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/180021