ArticleMolecules and cells2015
Raloxifene induces autophagy-dependent cell death in breast cancer cells via the activation of AMP-activated protein kinase.
Article in Molecules and cells, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Raloxifene suppresses growth and promotes intrinsic apoptotic signaling in C6 glioma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Design, Synthesis, Analysis, and Cytotoxicity of Novel Heteroaryl Derivatives of Dipyridothiazines.Current issues in molecular biology · 2026Article
- The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.International journal of molecular sciences · 2024Review
- Modulation of Breast Cancer Cell Apoptosis and Macrophage Polarization by Mistletoe Lectin in 2D and 3D Models.International journal of molecular sciences · 2024Article
- VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology.Frontiers in cell and developmental biology · 2024Review
- Article
- Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells.Drug delivery · 2022Article
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- Açai (Molecules (Basel, Switzerland) · 2021Article
- High-throughput screening for natural compound-based autophagy modulators reveals novel chemotherapeutic mode of action for arzanol.Cell death & disease · 2021Article
- Article
- Structural Characterization, Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine.Molecules (Basel, Switzerland) · 2021Article
- Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.Current research in pharmacology and drug discovery · 2021Review
- AutophagySMDB: a curated database of small molecules that modulate protein targets regulating autophagy.Autophagy · 2019Article
- The multifaceted role of autophagy in cancer and the microenvironment.Medicinal research reviews · 2019Review
- How does estrogen work on autophagy?Autophagy · 2019Review
- Adenine Inhibits the Growth of Colon Cancer Cells via AMP-Activated Protein Kinase Mediated Autophagy.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Article
- Vitamin E TPGS based transferosomes augmented TAT as a promising delivery system for improved transdermal delivery of raloxifene.PloS one · 2019Article
- Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Review
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11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the estrogen receptor (ER), and exhibits potent anti-tumor and autophagy-inducing effects in breast cancer cells. However, the mechanism of raloxifene-induced cell death and autophagy is not well-established. So, we analyzed mechanism underlying death and autophagy induced by raloxifene in MCF-7 breast cancer cells. Treatment with raloxifene significantly induced death in MCF-7 cells. Raloxifene accumulated GFP-LC3 puncta and increased the level of autophagic marker proteins, such as LC3-II, BECN1, and ATG12-ATG5 conjugates, indicating activated autophagy. Raloxifene also increased autophagic flux indicators, the cleavage of GFP from GFP-LC3 and only red fluorescence-positive puncta in mRFP-GFP-LC3-expressing cells. An autophagy inhibitor, 3-methyladenine (3-MA), suppressed the level of LC3-II and blocked the formation of GFP-LC3 puncta. Moreover, siRNA targeting BECN1 markedly reversed cell death and the level of LC3-II increased by raloxifene. Besides, raloxifene-induced cell death was not related to cleavage of caspases-7, -9, and PARP. These results indicate that raloxifene activates autophagy-dependent cell death but not apoptosis. Interestingly, raloxifene decreased the level of intracellular adenosine triphosphate (ATP) and activated the AMPK/ULK1 pathway. However it was not suppressed the AKT/mTOR pathway. Addition of ATP decreased the phosphorylation of AMPK as well as the accumulation of LC3-II, finally attenuating raloxifene-induced cell death. Our current study demonstrates that raloxifene induces autophagy via the activation of AMPK by sensing decreases in ATP, and that the overactivation of autophagy promotes cell death and thereby mediates the anti-cancer effects of raloxifene in breast cancer cells.
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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.