ArticleOncotarget2017
Thalidezine, a novel AMPK activator, eliminates apoptosis-resistant cancer cells through energy-mediated autophagic cell death.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- AMPK: The energy sensor at the crossroads of aging and cancer.Seminars in cancer biology · 2024Review
- Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.Acta pharmacologica Sinica · 2023Article
- An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2.Molecules (Basel, Switzerland) · 2021Article
- Review
- Autophagy Paradox of Cancer: Role, Regulation, and Duality.Oxidative medicine and cellular longevity · 2021Review
- Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism.Cell death & disease · 2020Article
- Characterisation of the developing heart in a pressure overloaded model utilising RNA sequencing to direct functional analysis.Journal of anatomy · 2020Article
- Anti-inflammatory Property of AMP-activated Protein Kinase.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Cancer Stem Cells as a Potential Target to Overcome Multidrug Resistance.Frontiers in oncology · 2020Review
- AMPK Activation of Apoptotic Markers in Human Breast Cancer Cell Lines with Different p53 Backgrounds: MCF-7, MDA-MB-231 and T47D Cells.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- The good, the bad and the autophagosome: exploring unanswered questions of autophagy-dependent cell death.Cell death and differentiation · 2019Review
- Novel chemotherapeutic agent, FND-4b, activates AMPK and inhibits colorectal cancer cell proliferation.PloS one · 2019Article
- Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells.Cell death & disease · 2018Article
- [2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- 2-Aminoethoxydiphenylborane sensitizes anti-tumor effect of bortezomib via suppression of calcium-mediated autophagy.Cell death & disease · 2018Article
- A Method for Rapid Screening of Anilide-Containing AMPK Modulators Based on Computational Docking and Biological Validation.Frontiers in pharmacology · 2018Article
- Dried Rehmannia root protects against glutamate-induced cytotoxity to PC12 cells through energy metabolism-related pathways.Neural regeneration research · 2017Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers. Here, we unravelled that the bisbenzylisoquinoline alkaloid thalidezine is a novel direct AMPK activator by using biolayer interferometry analysis and AMPK kinase assays. The quantification of autophagic EGFP-LC3 puncta demonstrated that thalidezine increased autophagic flux in HeLa cancer cells. In addition, metabolic stress assay confirmed that thalidezine altered the energy status of our cellular model. Remarkably, thalidezine-induced autophagic cell death in HeLa or apoptosis-resistant DLD-1 BAX-BAK DKO cancer cells was abolished by addition of autophagy inhibitor (3-MA) and AMPK inhibitor (compound C). The mechanistic role of autophagic cell death in resistant cancer cells was further supported through the genetic removal of autophagic gene7 (Atg7). Overall, thalidezine is a novel AMPK activator which has great potential to be further developed into a safe and effective intervention for apoptosis- or multidrug-resistant cancers.
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