ArticleDrug design, development and therapy2015
Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells.
Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 115 citations in OpenAlex.
- Phytochemicals Modulating Redox Homeostasis in Head and Neck Cancer.Cell biochemistry and biophysics · 2026Review
- Targeting the Correa's cascade of gastric cancer: the potential role of phytochemicals and autophagy modulation.Frontiers in pharmacology · 2026Review
- Quercetin Induces Apoptosis Through Downregulating P4HA2 and Inhibiting the PI3K/Akt/mTOR Axis in Hepatocellular Carcinoma Cells: An In Vitro Study.Cancer reports (Hoboken, N.J.) · 2025Article
- Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-naphthoquinone Hybrids.Current medicinal chemistry · 2025Article
- Molecular Mechanisms of the Therapeutic Effect of Selenium Nanoparticles in Hepatocellular Carcinoma.Cells · 2024Review
- Article
- Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (Review).International journal of molecular medicine · 2023Review
- Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Autophagy Inhibits Inflammation via Down-Regulation of p38 MAPK/mTOR Signaling Cascade in Endothelial Cells.Clinical, cosmetic and investigational dermatology · 2023Article
- Plumbagin Enhances the Anticancer Effects of PF Chemotherapy via Downregulation of the PI3K/AKT/mTOR/p70S6K Pathway in Human Tongue Squamous Cell Carcinoma.Journal of oncology · 2023Article
- Chemoselective Synthesis of Mannich Adducts from 1,4-Naphthoquinones and Profile as Autophagic Inducers in Oral Squamous Cell Carcinoma.Molecules (Basel, Switzerland) · 2022Article
- Biologically synthesized black ginger-selenium nanoparticle induces apoptosis and autophagy of AGS gastric cancer cells by suppressing the PI3K/Akt/mTOR signaling pathway.Journal of nanobiotechnology · 2022Article
- Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers.Cancer cell international · 2022Review
- Inhibition of Autophagy Promotes Hemistepsin A-Induced Apoptosis via Reactive Oxygen Species-Mediated AMPK-Dependent Signaling in Human Prostate Cancer Cells.Biomolecules · 2021Article
- Promising Anticancer Activities ofNutrients · 2021Review
- Hirudo (Leech) for proliferative vitreous retinopathy: A protocol for systemic review and meta-analysis.Medicine · 2021Article
- Plumbagin Enhances the Radiosensitivity of Tongue Squamous Cell Carcinoma Cells via Downregulating ATM.Journal of oncology · 2021Article
- AKIP1 promotes tumor progression by cancer-related pathways and predicts prognosis in tongue squamous cell carcinoma.American journal of translational research · 2021Article
- Regression of Melanoma Following Intravenous Injection of Plumbagin Entrapped in Transferrin-Conjugated, Lipid-Polymer Hybrid Nanoparticles.International journal of nanomedicine · 2021Article
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone; PLB), a naturally occurring naphthoquinone isolated from the roots of Plumbaginaceae plants, has been reported to possess anticancer activities in both in vitro and in vivo studies, but the effect of PLB on tongue squamous cell carcinoma (TSCC) is not fully understood. This study aimed to investigate the effects of PLB on cell cycle distribution, apoptosis, and autophagy, and the underlying mechanisms in the human TSCC cell line SCC25. The results have revealed that PLB exerted potent inducing effects on cell cycle arrest, apoptosis, and autophagy in SCC25 cells. PLB arrested SCC25 cells at the G2/M phase in a concentration- and time-dependent manner with a decrease in the expression level of cell division cycle protein 2 homolog (Cdc2) and cyclin B1 and increase in the expression level of p21 Waf1/Cip1, p27 Kip1, and p53 in SCC25 cells. PLB markedly induced apoptosis and autophagy in SCC25 cells. PLB decreased the expression of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) while increasing the expression level of the pro-apoptotic protein Bcl-2-associated X protein (Bax) in SCC25 cells. Furthermore, PLB inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), and p38 mitogen-activated protein kinase (p38 MAPK) pathways as indicated by the alteration in the ratio of phosphorylation level over total protein expression level, contributing to the autophagy inducing effect. In addition, we found that wortmannin (a PI3K inhibitor) and SB202190 (a selective inhibitor of p38 MAPK) strikingly enhanced PLB-induced autophagy in SCC25 cells, suggesting the involvement of PI3K- and p38 MAPK-mediated signaling pathways. Moreover, PLB induced intracellular reactive oxygen species (ROS) generation and this effect was attenuated by l-glutathione (GSH) and n-acetyl-l-cysteine (NAC). Taken together, these results indicate that PLB promotes cellular apoptosis and autophagy in TSCC cells involving p38 MAPK- and PI3K/Akt/mTOR-mediated pathways with contribution from the GSK3β and ROS-mediated pathways.
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