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Polypharmacological Profiles Underlying the Antitumor Property of
Li Tao1,2, Min Xu1,2, Xiaojun Dai1,2,3
1College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, China.
Oxidative Medicine and Cellular Longevity
|September 14, 2018
Summary
Danshen, a traditional Chinese herb, inhibits cancer metastasis by suppressing neutrophil extracellular traps (NETs). Key compounds, salvianolic acid B and 15,16-dihydrotanshinone I, block NET formation, offering a novel therapeutic strategy for metastatic cancers.
Area of Science:
- Herbal Medicine
- Cancer Biology
- Immunology
Background:
- Danshen (Salvia miltiorrhiza) is a well-researched medicinal herb with antioxidant, anti-inflammatory, and anticoagulant properties.
- Neutrophil extracellular traps (NETs) are increasingly implicated in the pathology of metastatic cancers.
Purpose of the Study:
- To investigate the hypothesis that Danshen's anti-metastatic effects are mediated by the suppression of NET formation.
- To identify active compounds in Danshen responsible for inhibiting NETs and elucidate their mechanisms of action.
Main Methods:
- An experimental pulmonary metastasis model using RFP-labeled gastric cancer cells and live-imaging.
- Assays for NET formation in human neutrophils induced by PMA.
- Screening of Danshen fractions and active compounds (salvianolic acid B, 15,16-dihydrotanshinone I).
- Biochemical assays to determine the targets of active compounds (MPO, NADPH oxidase).
Main Results:
- Danshen treatment reduced metastatic nodule formation and neutrophil infiltration in a mouse model.
- Salvianolic acid B and 15,16-dihydrotanshinone I significantly inhibited PMA-induced NET formation and reduced citrullinated histone H3 levels.
- Salvianolic acid B blocked myeloperoxidase activity, while 15,16-dihydrotanshinone I inhibited NADPH oxidase.
- Combined treatment with salvianolic acid B and 15,16-dihydrotanshinone I showed synergistic inhibition of NET formation.
Conclusions:
- Danshen effectively reduces cancer metastasis, partly through the inhibition of NET formation.
- Salvianolic acid B and 15,16-dihydrotanshinone I are key active compounds that target distinct pathways in NET formation.
- These findings suggest a novel therapeutic approach targeting NETs for managing hematogenous metastasis of certain cancers.
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