ArticleOncotarget2016
Autophagy induction causes a synthetic lethal sensitization to ribonucleotide reductase inhibition in breast cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Bactericidal Metal-Organic Gallium Frameworks - Synthesis to Application.Molecular pharmaceutics · 2025Review
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO.Journal of fungi (Basel, Switzerland) · 2023Article
- Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.World journal of clinical cases · 2022Article
- Article
- Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.Annual review of biochemistry · 2020Review
- The Antitumor Didox Acts as an Iron Chelator in Hepatocellular Carcinoma Cells.Pharmaceuticals (Basel, Switzerland) · 2019Article
- Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction.Communications biology · 2018Article
- Autophagy mediates free fatty acid effects on MDA-MB-231 cell proliferation, migration and invasion.Oncology letters · 2017Article
- Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer.Cell death discovery · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Macroautophagy can promote cellular survival or death depending on the cellular context and its extent. We hypothesized that autophagy induction would synergize with a therapeutic agent targeting the autophagic cargo. To test this hypothesis, we treated breast cancer MDA-MB-231 cells with tamoxifen (TMX), which induces autophagy through an estrogen receptor-independent pathway. Induction of autophagy reduced cellular levels of RRM2, a subunit of ribonucleotide reductase (RR), the rate limiting enzyme in the production of deoxyribonucleotide triphosphates (dNTPs). This autophagy inducer was combined with COH29, an inhibitor developed in our laboratory that targets RR through a novel mechanism. The combination therapy showed synergistic effects on cytotoxicity in vitro and in an in vivo xenograft model. This cytotoxicity was blocked by knockdown of the autophagy protein ATG5 or addition of chloroquine, an autophagy inhibitor. The combined therapy also induced dNTP depletion and massive genomic instability, leading us to hypothesize that combining autophagy induction with RR inhibition can lead to mitotic catastrophe in rapidly dividing cells. We propose that this TMX + COH29 combined therapy may have clinical benefit. Furthermore, autophagy induction may be a general mechanism for augmenting the effects of chemotherapeutic agents.
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Registered trials
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.