TY - JOUR
T1 - Astragalus Polysaccharide (PG2) Suppresses Macrophage Migration Inhibitory Factor and Aggressiveness of Lung Adenocarcinoma Cells
AU - Liao, Chien Huang
AU - Yong, Chen Yin
AU - Lai, Gi Ming
AU - Chow, Jyh Ming
AU - Cheng, Chieh Fang
AU - Fang, Chia Lang
AU - Lin, Pei Chun
AU - Chang, Chia Lun
AU - Zheng, Yu Mei
AU - Chuang, Shuang En
AU - Whang-Peng, Jacqueline
AU - Yao, Chih Jung
N1 - Funding Information:
This study was supported by a joint grant from Wan Fang Hospital, Taipei Medical University, and PhytoHealth Corporation, Taipei, Taiwan (Grant W397); Health and Welfare Surcharge of tobacco products (MOHW108-TDU-B-212-124020); and Ministry of Science and Technology, Taiwan (MOST107-2314-B-038-080-MY2). The authors would like to thank PhytoHealth Corporation (Taipei, Taiwan) for providing the lyophilized powder of injectable APS (PG2). This manuscript was edited by Wallace Academic Editing.
PY - 2020
Y1 - 2020
N2 - Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.
AB - Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.
KW - Astragalus membranaceus
KW - Epithelial-Mesenchymal Transition
KW - Lung Adenocarcinoma
KW - Macrophage Migration Inhibitory Factor
KW - PG2
KW - A549 Cells
KW - Cell Movement/drug effects
KW - Neoplasm Invasiveness
KW - Humans
KW - Injections, Intraperitoneal
KW - Polysaccharides/administration & dosage
KW - Cell Survival/drug effects
KW - Mice, SCID
KW - Intramolecular Oxidoreductases/metabolism
KW - Dose-Response Relationship, Drug
KW - Animals
KW - Lung Neoplasms/metabolism
KW - Epithelial-Mesenchymal Transition/drug effects
KW - Adenocarcinoma/metabolism
KW - Cell Proliferation/drug effects
KW - Phytotherapy
KW - Macrophage Migration-Inhibitory Factors/metabolism
KW - Astragalus propinquus/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85091771341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091771341&partnerID=8YFLogxK
U2 - 10.1142/S0192415X20500731
DO - 10.1142/S0192415X20500731
M3 - Article
C2 - 32924531
AN - SCOPUS:85091771341
SN - 0192-415X
VL - 48
SP - 1491
EP - 1509
JO - American Journal of Chinese Medicine
JF - American Journal of Chinese Medicine
IS - 6
ER -