Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling.

Abstract

Metastasis is the leading cause of death in breast cancer patients. Osthole, as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula, has shown a promising anti-metastatic activity in human breast cancer cells, but the underlying mechanisms remain ambiguous. In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model. We showed that the expression of integrin α3 (ITGα3) and integrin β5 (ITGβ5) was upregulated in highly metastatic MDA-MB-231, MDA-MB-231BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line, which might be the key targets of osthole's anti-metastatic action. Furthermore, we showed that knockdown of ITGα3 and ITGβ5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway, whereas overexpression of ITGα3 and ITGβ5 caused the opposite effects. Consistently, osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGβ5 signaling in vitro and in vivo. These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.

• Authors: Yue-Qiang Chen, Hai-Yan Song, Zhong-Yan Zhou, Jiao Ma, Zhan-Yang Luo, Ying Zhou, Jian-Yi Wang, Sheng Liu, Xiang-Hui Han
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 43 Issue 6 Pg. 1544-1555 (Jun 2022) ISSN: 1745-7254 [Electronic] United States
• PMID: 34426644 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to CPS and SIMM.

Chemical References

• Coumarins
• osthol

Topics

• Animals
• Breast Neoplasms (pathology)
• Cell Line, Tumor
• Cell Movement
• Coumarins (pharmacology, therapeutic use)
• Female
• Humans
• Neoplasm Invasiveness (prevention & control)
• Zebrafish