ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Combination of Asiatic Acid and Naringenin Modulates NK Cell Anti-cancer Immunity by Rebalancing Smad3/Smad7 Signaling.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 82 citations in OpenAlex.
- Reconstitution of Natural Killer cells after allogeneic hematopoietic stem cell transplantation is facilitated by Huiyang-Guben decoction through activating the Smad7/Stat3 signal pathway.Molecular and cellular biochemistry · 2024Trial
- Mechanisms of tumor cell evasion from NK cell-mediated killing and advances in NK cell-based cancer immunotherapy.Pharmaceutical science advances · 2026Review
- Micro-Nanoplastic Exposure and Lung Cancer Biomarkers: The Role of Extracellular Vesicle-Mediated Intercellular Communication.International journal of molecular sciences · 2026Review
- SMAD7 drives natural killer cell antitumor activity through canonical TGF-β blockade and non-canonical transcriptional activation of STAT5A.Journal for immunotherapy of cancer · 2026Article
- Citrus flavanones (naringenin, hesperidin, and hesperetin) in oral and gastric carcinogenesis: mechanistic insights into oxidative stress, cell death, epigenetic regulation, non-coding RNAs, and tumor microenvironment remodeling.Frontiers in cell and developmental biology · 2026Review
- Nanodelivery of Traditional Chinese Medicine Monomers: An Emerging Strategy to Reprogram the Immunosuppressive Tumor Microenvironment.International journal of nanomedicine · 2026Review
- Synergistic immunomodulatory effects of naringenin and photothermal therapy in triple-negative breast cancer.iScience · 2025Article
- Study on the Function ofAnimals : an open access journal from MDPI · 2025Article
- Genomic signal selection analysis reveals genes related to the lambing trait of Hotan sheep.Animal bioscience · 2025Article
- Research Progress of Natural Compounds from Chinese Herbal Medicine in the Treatment of Melanoma.Current treatment options in oncology · 2025Review
- Advances in research on flavonoids in tumor immunotherapy (Review).Molecular medicine reports · 2025Review
- Integration of active ingredients from traditional Chinese medicine with nano-delivery systems for tumor immunotherapy.Journal of nanobiotechnology · 2025Review
- Review
- The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.Pharmaceutics · 2024Review
- Asiatic acid inhibits HBV cccDNA transcription by promoting HBx degradation.Virology journal · 2024Article
- Article
- Disrupting Smad3 potentiates immunostimulatory function of NK cells against lung carcinoma by promoting GM-CSF production.Cellular and molecular life sciences : CMLS · 2024Article
- Can Asiatic Acid fromCancers · 2024Review
- Paulownin elicits anti-tumor effects by enhancing NK cell cytotoxicity through JNK pathway activation.Frontiers in pharmacology · 2024Article
- Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.Journal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β1 (TGF-β1) plays a promoting role in tumor growth via a mechanism associated with hyperactive Smad3 and suppressed Smad7 signaling in the tumor microenvironment. We report that retrieving the balance between Smad3 and Smad7 signaling with asiatic acid (AA, a Smad7 inducer) and naringenin (NG, a Smad3 inhibitor) effectively inhibited tumor progression in mouse models of invasive melanoma (B16F10) and lung carcinoma (LLC) by promoting natural killer (NK) cell development and cytotoxicity against cancer. Mechanistically, we found that Smad3 physically bound Id2 and IRF2 to suppress NK cell production and NK cell-mediated cytotoxicity against cancer. Treatment with AA and NG greatly inhibited Smad3 translation and phosphorylation while it restored Smad7 expression, and, therefore, it largely promoted NK cell differentiation, maturation, and cytotoxicity against cancer via Id2/IRF2-associated mechanisms. In contrast, silencing Id2 or IRF2 blunted the protective effects of AA and NG on NK cell-dependent anti-cancer activities. Thus, treatment with AA and NG produced an additive effect on inactivating TGF-β1/Smad3 signaling, and, therefore, it suppressed melanoma and lung carcinoma growth by promoting NK cell immunity against cancer via a mechanism associated with Id2 and IRF2.
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