Academic Journal
Salvianolic acid A inhibits tumor cell proliferation and induces chromosomal abnormalities by blocking the citrullinating enzyme PADs.
| Title: | Salvianolic acid A inhibits tumor cell proliferation and induces chromosomal abnormalities by blocking the citrullinating enzyme PADs. |
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| Authors: | Chen J; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China., Wang T; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China., Gao B; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China., Ke X; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China., Zhou X; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China. Electronic address: zhouxianglian@shutcm.edu.cn., Qu Y; Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China. Electronic address: yiqu@shutcm.edu.cn. |
| Source: | Life sciences [Life Sci] 2026 Aug 01; Vol. 398, pp. 124444. Date of Electronic Publication: 2026 May 08. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| MeSH Terms: | Cell Proliferation*/drug effects , Caffeic Acids*/pharmacology , Lactates*/pharmacology , Chromosome Aberrations*/chemically induced , Chromosome Aberrations*/drug effects, Citrulline/metabolism ; Histones/metabolism ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Molecular Docking Simulation |
| Abstract: | Aims: Citrullination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), is closely linked to cancer progression. Despite PADs' clinical importance, effective inhibitors are urgently needed. We aimed to identify a novel PAD inhibitor, salvianolic acid A (SAA), and to characterize the mechanism by which SAA inhibits PAD activity and exerts anti-tumor effects. Materials and Methods: Citrullination of histone H3 (CitH3), drug affinity responsive target stability (DARTS) assays, in vitro enzymatic activity, and molecular docking were used to investigate SAA's direct interaction with PAD family members. PAD oligomerization was evaluated by disuccinimidyl suberate (DSS) cross-linking, native PAGE, and proximity ligation assay (PLA). PAD-histone H3 interaction was assessed by co-immunoprecipitation and PLA. Cellular effects were evaluated in colorectal cancer cell lines and mouse intestinal organoids using CCK-8, Transwell, EdU, and karyotype analyses. Key Findings: SAA was identified as a reversible pan-PAD inhibitor that binds directly to PAD1, PAD2, PAD3, and PAD4. Unlike traditional covalent inhibitors, SAA promotes PAD oligomerization and enhances PAD-histone H3 interaction while inhibiting histone H3 citrullination. SAA significantly inhibited cancer cell proliferation, migration, and organoid growth, and induced numerical chromosomal abnormalities in a PAD2/4-dependent manner. Significance: These findings establish PADs as functional targets of SAA and reveal a novel mechanism for PAD inhibition, positioning SAA as a promising chemical probe for treating citrullination-related diseases. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: Citrullination; Inhibition; PAD; Salvianolic acid a |
| Substance Nomenclature: | 0 (Caffeic Acids) 51622542XO (salvianolic acid A) 0 (Lactates) 29VT07BGDA (Citrulline) 0 (Histones) |
| Entry Date(s): | Date Created: 20260510 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.lfs.2026.124444 |
| PMID: | 42107692 |
| Database: | MEDLINE |
| ISSN: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2026.124444 |