ArticlePloS one2015
Cucurbitacin E Induces Autophagy via Downregulating mTORC1 Signaling and Upregulating AMPK Activity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Cucurbitacin E Glucoside as an Apoptosis Inducer in Melanoma Cancer Cells by Modulating AMPK/PGK1/PKM2 Pathway.Anti-cancer agents in medicinal chemistry · 2025Article
- Cucurbitacin E Exerts Anti-Proliferative Activity via Promoting p62-Dependent Apoptosis in Human Non-Small-Cell Lung Cancer A549 Cells.Current issues in molecular biology · 2023Article
- Pharmacokinetics and Biological Activity of Cucurbitacins.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights.Cells · 2022Review
- Antioxidants profile ofFood chemistry. Molecular sciences · 2021Article
- The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer.Cancer medicine · 2021Article
- AMPK/mTOR/ULK1 Axis-Mediated Pathway Participates in Apoptosis and Autophagy Induction by Oridonin in Colon Cancer DLD-1 Cells.OncoTargets and therapy · 2020Article
- Anti-inflammatory Property of AMP-activated Protein Kinase.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Plant triterpenoid saponins: biosynthesis, in vitro production, and pharmacological relevance.Protoplasma · 2019Review
- Cucurbitacins extracted from Cucumis melo L. (CuEC) exert a hypotensive effect via regulating vascular tone.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation.International journal of oncology · 2019Article
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- The cucurbitacins D, E, and I fromIranian journal of basic medical sciences · 2018Article
- Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway.Oncology letters · 2018Article
- Cucurbitacin E induces apoptosis of human prostate cancer cells via cofilin-1 and mTORC1.Oncology letters · 2017Article
- Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway.PloS one · 2017Article
- Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade.Integrative cancer therapies · 2016Article
- Triterpenes in cancer: significance and their influence.Molecular biology reports · 2016Review
- New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy.Molecules (Basel, Switzerland) · 2016Review
- Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway.International journal of molecular medicine · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cucurbitacins, the natural triterpenoids possessing many biological activities, have been reported to suppress the mTORC1/p70S6K pathway and to induce autophagy. However, the correlation between such activities is largely unknown. In this study, we addressed this issue in human cancer cells in response to cucurbitacin E (CuE) treatment. Our results showed that CuE induced autophagy as evidenced by the formation of LC3-II and colocalization of punctate LC3 with the lysosomal marker LAMP2 in HeLa and MCF7 cells. However, CuE induced much lower levels of autophagy in ATG5-knocked down cells and failed to induce autophagy in DU145 cells lacking functional ATG5 expression, suggesting the dependence of CuE-induced autophagy on ATG5. Consistent with autophagy induction, mTORC1 activity (as reflected by p70S6K and ULK1S758 phosphorylation) was inhibited by CuE treatment. The suppression of mTORC1 activity was further confirmed by reduced recruitment of mTOR to the lysosome, which is the activation site of mTORC1. In contrast, CuE rapidly activated AMPK leading to increased phosphorylation of its substrates. AMPK activation contributed to CuE-induced suppression of mTORC1/p70S6K signaling and autophagy induction, since AMPK knockdown diminished these effects. Collectively, our data suggested that CuE induced autophagy in human cancer cells at least partly via downregulation of mTORC1 signaling and upregulation of AMPK activity.
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