ArticleDrug development research2022
Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells.
Article in Drug development research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Pyroptosis as a double-edged sword in colorectal cancer: Molecular mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Overexpression of Forsythia intermedia pinoresinol lariciresinol reductase gene in Sesamum indicum increases secoisolariciresinol diglucoside content.Transgenic research · 2026Article
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination.Cancer biology & therapy · 2025Article
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
- Esketamine mitigates endotoxin-induced acute lung injury by suppressing caspase-11-driven pyroptosis.BMC anesthesiology · 2025Article
- The Role of Pyroptosis in Colorectal Cancer: From Mechanisms to Therapeutic Opportunities.Cancer management and research · 2025Review
- Lignans: Advances in Biosynthesis, Bioavailability, and Pharmacological Activity.Combinatorial chemistry & high throughput screening · 2025Review
- Pyroptosis in health and disease: mechanisms, regulation and clinical perspective.Signal transduction and targeted therapy · 2024Review
- Research progress on the effect of pyroptosis on the occurrence, development, invasion and metastasis of colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- Review
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy.Cell death discovery · 2024Review
- Pyroptosis and inflammasomes in cancer and inflammation.MedComm · 2023Review
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Effect of caspase-1 (Translational cancer research · 2023Article
- Pyroptosis Modulators: New Insights of Gasdermins in Health and Disease.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secoisolariciresinol diglucoside (SDG) is the main component of lignans with various biological activities, including anticancer activity. However, whether SDG has obvious anticancer effects on colorectal cancer (CRC) is unclear. Pyroptosis, a form of programmed cell death, has received increasing attention in cancer-related research. In this study, we aimed to test the anticancer properties and relatecd functional mechanisms of SDG. we found that SDG not only inhibited the cell viability of HCT116 cells, but also induced HCT116 cells to swell with apparent large bubbles, which are typical signs of pyroptosis. Furthermore, SDG induced cell pyroptosis by enhancing cleavage of the N-terminal fragment of gasdermin D (GSDMD) in CRC cells, accompanied by increased caspase-1 cleavage. Consistent with this, SDG-induced GSDMD-N-terminal fragment cleavage and pyroptosis were reduced by siRNA-mediated silencing of caspase-1 or treatment with the specific caspase-1 inhibitor VX-765 treatment, suggesting that active caspase-1 further induces pyroptosis. A mechanistic study showed that SDG induced reactive oxygen species (ROS) accumulation and inhibits phosphatidylinositol 3-kinase (PI3K) phosphorylation and increases pyroptosis, while increasing GSDMD and caspase-1 cleavage and enhancing expression of BCL2-associated X (BAX), which could be rescued by the ROS scavenger (NAC), suggesting that SDG-induced GSDME-dependent pyroptosis is related to the ROS/PI3K/AKT/BAX-mitochondrial apoptotic pathway. In vivo results showed that SDG significantly inhibited tumor growth and induced pyroptosis in the HCT116-CRC nude mouse model. In conclusion, our findings suggest that the anticancer activity of SDG in CRC is associated with the induction of GSDMD-dependent pyroptosis by SDG through the generation of ROS/P13K/AKT/BAK-mitochondrail apoptosis pathway, providing insights into SDG in its potential new application in cancer treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.