Rosmarinic acid inhibits stem-like breast cancer through hedgehog and Bcl-2/Bax signaling pathways

Pharmacognosy Magazine ,2019,15,65,600-606.DOI:10.4103/pm.pm_22_19Published:September 2019Type:Original Article Authors:Hong Li, Yuefeng Zhang, Hsiao-Huei Chen, En Huang, Hailin Zhuang, Dan Li, and Feng Ni Author(s) affiliations:Hong Li1, Yuefeng Zhang2, Hsiao-Huei Chen3, En Huang3, Hailin Zhuang1, Dan Li1, Feng Ni2 1Department of Health Management, Fujian Health College, Fuzhou, Fujian, China 2Medical Technology Center, Fujian Health College, Fuzhou, Fujian, China 3Department of Medicine, Brain and Mind Institute, University of Ottawa, Ottawa, Canada Abstract:Background: Rosmarinic acid (RA) is a natural phenolic acid present in various Lamiaceae herbs. RA shows anti-tumor effects on many tumors but has yet to be tested on triple negative breast cancer and its derived breast cancer stem-like cells (BCSCs). Objective: This study aimed to detect whether RA could inhibit the proliferation and migration of BCSCs through hedgehog (Hh) signaling while promoting apoptosis via Bcl-2/Bax. Materials and Methods: BCSCs from the human breast cancer cell line MD-MB-231 were isolated by fluorescence-activated cell sorting with the surface markers of CD44*/CD24-/low. The viability, migration, and apoptosis of BCSCs were assessed by the CCK-8 assay, cell wound healing test, and flow cytometry for positive staining for Annexin V-FITC and propidium iodine (PI), respectively. mRNA and protein levels of Hh and Bcl-2/Bax signaling pathways were obtained by real-time reverse transcriptase polymerase chain reaction and immunoblots. Results: RA inhibited the viability and migration of BCSCs and increased the numbers of late apoptotic cells. Consistent with the increased apoptosis, RA treatment downregulated Bcl-2 while upregulating Bax expression. In line with its effect to limit migration, RA treatment inhibited the expression of Hh-related genes smoothened and glioma-associated oncogene homolog 1. Conclusion: The present study suggests that RA exerts anti-cancer effects on BCSCs by inhibiting Bcl-2 and Hh signaling pathways. Keywords:Bax, Bcl-2, breast cancer stem-like cells, hedgehog signaling pathway, rosmarinic acidView:PDF (2.29 MB)