Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase
Open accessAbstract
BACKGROUND: Ligustrazine, active ingredients extracted from the natural herb Ligusticum Chuanxiong Hort, has promising anti-tumor properties on tumor cell lines. However, the potential anti-tumor activity of ligustrazine on colorectal cancer (CRC) cells and the molecular mechanisms have not been elucidated. In this study, we explored the critical functions of ligustrazine on SW480 and CT26 cells at cellular levels. METHODS: CCK-8 assay was performed to analyze the cell viability. Flow cytometry analysis was applied to study cell apoptosis and cell cycle. The expressions of cell apoptosis and cell cycle-associated proteins were conducted by western blot and qRT-PCR analysis. RESULTS: Ligustrazine showed significant inhibitory effects on the proliferation of SW480 and CT26 cells. Ligustrazine induced cell apoptosis was associated with the up-regulation of pro-apoptotic protein and the down-regulation of anti-apoptotic protein in an activated mitochondrial-dependent pathway. And it indicated that ligustrazine induced cell cycle arrest by changing the cell cycle distribution, which leads to cell cycle arrest at the G0/G1 phase. Besides, the ligustrazine-induced cell apoptosis and cell cycle arrest were markedly reversed by pifithrin-α (p53 inhibitor), which suggested that ligustrazine-induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase. CONCLUSIONS: These findings demonstrated that ligustrazine could induce SW480 and CT26 cells apoptosis via a p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase. Ligustrazine may serve as a potential anti-cancer agent for CRC.
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The clinical efficacy of MDM2 inhibitors may mainly rely on reversible cell cycle arrest rather than direct induction of cell death through p53-dependent signaling pathway.
“Therefore, the clinical efficacy of MDM2 inhibitors may mainly rely on the reversible cell cycle arrest rather than direct induction of cell death through p53-dependent signaling pathway [89–91].”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [89]
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Self-citation
- Authors
- Bian, Y., Yang, L., Sheng, W., Li, Z., Xu, Y., Li, W., & Zeng, L.
- Affiliations
- Nanjing University of Chinese Medicine (CN)
- Corresponding author
- Zeng, Li
- Venue
- Annals of Palliative Medicine
- Publisher
- AME Publishing Company
- Published
- 2021-02
- Volume
- 10
- Issue
- 2
- Pages
- 1578-1588
- ISSN
- 2224-5820 (ISSN-L)
- 2224-5839
- OpenAlex
- W3107603624
- Cited by
- 23
- References
- 32
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 1
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Annals of Palliative Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Massachusetts Department of Agricultural Resources
- National Natural Science Foundation of China (81673982, 81603529, 81704084, 16KJB360002)
- Government of Jiangsu Province
- China Scholarship Council
- Nanjing University of Chinese Medicine (81704084)
- Nanjing University
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Qinglan Project of Jiangsu Province of China (81704084, 81603529, 2019YSHL005, 81673982, 16KJB360002)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- tetramethylpyrazine, colorectal cancer, apoptosis, p53, mitochondrial apoptosis, G0/G1 cell cycle arrest, pifithrin-alpha, Ligusticum chuanxiong, anticancer activity, SW480 cells, CT26 cells, cell proliferation inhibition
- MeSH terms
- Humans, Pyrazines, Colorectal Neoplasms, Signal Transduction, Tumor Suppressor Protein p53, G1 Phase, Apoptosis, Cell Proliferation, Cell Cycle Checkpoints
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