Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling

Nie，Xin1,2; Fu，Li1; Cheng，Yanfen1; Wu，Xiaoping3; Lv，Kongpeng4; Li，Renkai3; Wu，Yihan1; Leung，George Pak Heng3; Fu，Chaomei1; Lee，Simon Ming Yuen2; Seto，Sai Wang5,6; Zhang，Jinming1; Li，Jingjing6,7

2023

10.1002/ptr.7909

Phytotherapy Research   Impact Factor & Quartile

0951-418X

1099-1573

Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-γ-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway.

breast cancer metastasis Garcinone E STAT6 signaling tumor-associated macrophages

SCI

English

Others

WOS:000999224400001

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85161360448

Scopus

1.State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China
2.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences,University of Macau,Macao
3.Department of Pharmacology and Pharmacy,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong
4.Department of Interventional Radiology,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
5.Department of Food Science and Nutrition,Faculty of Science,Hong Kong Polytechnic University,Hong Kong
6.The Research Center for Chinese Medicine Innovation,Hong Kong Polytechnic University,Hong Kong
7.Department of Rehabilitation Sciences,Faculty of Health and Social Sciences,Hong Kong Polytechnic University,Hong Kong

Nie，Xin,Fu，Li,Cheng，Yanfen,et al. Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling[J]. Phytotherapy Research,2023.

Nie，Xin.,Fu，Li.,Cheng，Yanfen.,Wu，Xiaoping.,Lv，Kongpeng.,...&Li，Jingjing.(2023).Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling.Phytotherapy Research.

Nie，Xin,et al."Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling".Phytotherapy Research (2023).