Tumorigenic risk of Angelica sinensis on ER-positive breast cancer growth through ER-induced stemness in vitro and in vivo
Authors: Yi Wen
Hongni Zhu
Jianping Chen
Lei Jia
Fei Gao
Jeishu You
Kumar Ganesan
Journal: Journal of Ethnopharmacology (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Angelica sinensis; Breast cancer; Cancer stem cells; Estrogen receptor-positive; Unsafe.
Affiliations: School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen Virtual University Park, Nanshan, Shenzhen, China. Electronic address: ., School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen Virtual University Park, Nanshan, Shenzhen, China., School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong., School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen Virtual University Park, Nanshan, Shenzhen, China; Guangzhou University of Chinese Medicine, Daxuecheng Hongmian Road, Panyu District, Guangzhou, Guangdong Province, China. Electronic address: .

Abstract:  Ethnopharmacological relevance: The root of Angelica sinensis is widely used in traditional Chinese Medicine for relieving gynecological discomforts among the women population. However, its hormone-like effects have raised great attention on whether it is appropriate to use in breast cancer (BC) patients. Hence, this study aimed to investigate the tumorigenic effect of aqueous root extract of Angelica sinensis (AS) on estrogen receptor (ER)-positive BC growth through ER-induced stemness in-vitro and in-vivo. Materials and methods: The chemical composition of the AS was characterized by HPLC. Cell viability was detected by MTS assay. The in-vivo effect of AS was investigated by xenograft model, immunohistochemistry, histology, Western blot, and self-renewal ability assay. Target verification was used by shRNA construction and transfection. Mammosphere formation assay was performed by flow cytometry. Results: AS significantly promoted the proliferation of MCF-7 cells and inhibited the growth of MDA-MB-231 cells. AS significantly induced tumor growth (2.5 mg/kg) in xenograft models and however tamoxifen treatment significantly suppressed the AS-induced tumor growth. AS induced ERα expression in both in-vivo and in-vitro and promoted cancer stem cell activity in ER-positive BC. Conclusion: AS shows the tumorigenic potential on ER-positive BC growth through ERα induced stemness, suggesting that the usage of AS is not recommended for BC in terms of safety measures. 

Retracted: No

PubPeer comments:
 Figure 7: Part B, there appear to be some splices in the top row that aren t present in the rows beneath, I ve added the yellow squares to show where I mean. Could the authors share the raw data, i.e. the scans of the blots? Figure 7: Part C, the ERu03b1 histology images show a stretched subsection of the CD44 histology images. No magnification is given, little information in the methods to help understand what has happened here. I ve added the red and blue rectangles to show the overlaps. Could the authors comment? ![file] , 
 #1 Dear Editor: Thank you for queries related to our publication in the Journal of Ethnopharmacology. The following is a point-by-point response to the Editoru2019s comments. Comments 1. Figure 7: Part B, there appear to be some splices in the top row that aren t present in the rows beneath, I ve added the yellow squares to show where I mean. Could the authors share the raw data, i.e. the scans of the blots? u2022tOne of our master students, Hongni Zhu (first author) had performed the in vitro and in vivo experiments and she had left after her graduation without submitting any raw data. However, we again performed the test and the outcome has been enclosed as PPT and BioRad image. Comments 2. Figure 7: Part C, the ERu03b1 histology images show a stretched subsection of the CD44 histology images. No magnification is given, little information in the methods to help understand what has happened here. I ve added the red and blue rectangles to show the overlaps. Could the authors comment? ![](http: ) u2022tAs shown in Fig 7C. AS increased CD44 and ERu03b1 expression in mammary tumor tissues of MCF7 xenograft nude mice when compared to the control group. The red staining indicated the high expression of respective CD44 and ERu03b1. The blue staining indicated the nuclei. Representative pictures of cells were taken by a bright-field microscope at 10x magnification. ![](http: ) , 
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