Ursolic acid inhibits proliferation, migration and invasion of human papillary thyroid carcinoma cells via CXCL12/CXCR4/CXCR7 axis through cancer-associated fibroblasts

As a pentacyclic triterpenoid compound, Ursolic acid (UA) broads range of biological effects. CXCL12 is a ligand for CXCR4 and CXCR7 proteins on thyroid cancer cells. Here we examined the effects of UA on the proliferation, migration and invasion of papillary thyroid carcinoma (PTCs) in a dose-manne...

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Bibliographic Details
Published in:Human & experimental toxicology 2022-06, Vol.41, p.9603271221111333
Main Authors: Cao, Xianjiao, He, Qingqing
Format: Article
Language:English
Subjects:
Biological effects
Cancer
Cancer-Associated Fibroblasts - metabolism
Cancer-Associated Fibroblasts - pathology
Cell culture
Cell Movement
Cell Proliferation
Chemokine CXCL12 - pharmacology
Chemopreventive agents
CXCL12 protein
CXCR4 protein
Fibroblasts
Humans
Papillary thyroid carcinoma
Receptors, CXCR
Receptors, CXCR4
Thyroid
Thyroid cancer
Thyroid Cancer, Papillary - drug therapy
Thyroid Neoplasms - drug therapy
Thyroid Neoplasms - metabolism
Triterpenes - pharmacology
Ursolic Acid
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Summary:As a pentacyclic triterpenoid compound, Ursolic acid (UA) broads range of biological effects. CXCL12 is a ligand for CXCR4 and CXCR7 proteins on thyroid cancer cells. Here we examined the effects of UA on the proliferation, migration and invasion of papillary thyroid carcinoma (PTCs) in a dose-manner. In addition, UA can reduce the expression levels of CXCR4 and CXCR7 in PTCs. In addition to this direct anticancer pathway, studies have shown that UA can play an anticancer role by affecting the secretion of CXCL12 in cancer-associated fibroblasts (CAFs). After treated with UA, normal fibroblasts and CAFs culture medium (CM) showed differential CXCL12 expression levels. We prepared fibroblast conditioned medium according to the intervention of UA, then cultured TPC-1 and B-CPAP cells with differential CM, and detected significant differences in the proliferation, migration and invasion of cancer cells. Our findings uncovered an indirect anticancer mechanism of UA. This cancer chemopreventive properties is expected to make UA a clinically useful chemopreventive agent.
ISSN:0960-3271
1477-0903
DOI:10.1177/09603271221111333