ArticleBritish journal of pharmacology2013
Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Global pattern and evolution of PPARγ in breast cancer: a 25-Year bibliometric and visualized knowledge map analysis.Frontiers in oncology · 2026Pooled it
- Chemotherapy-induced cardiotoxicity in breast cancer: mechanisms, diagnostic advances, and emerging protective strategies.American journal of physiology. Heart and circulatory physiology · 2025Review
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- Thiazolidinedione derivatives in cancer therapy: exploring novel mechanisms, therapeutic potentials, and future horizons in oncology.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- Effects of an L-Leucine-Rich Diet on Liver and Kidneys in a Doxorubicin Toxicity Model.Life (Basel, Switzerland) · 2023Article
- A Cross-Talk about Radioresistance in Lung Cancer-How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies.International journal of molecular sciences · 2023Review
- The role of circadian clocks in cancer: Mechanisms and clinical implications.Genes & diseases · 2023Review
- CDDO, a PPAR-γ ligand, inhibits TPA-induced cell migration and invasion through a PPAR-γ-independent mechanism.Oncology letters · 2022Article
- Anthracycline-free tumor elimination in mice leads to functional and molecular cardiac recovery from cancer-induced alterations in contrast to long-lasting doxorubicin treatment effects.Basic research in cardiology · 2021Article
- Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells.Molecular diversity · 2021Article
- Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights.Medicinal research reviews · 2018Review
- Stimulatory Effect of Indolic Hormone on AsInternational journal of molecular and cellular medicine · 2018Article
- Cell death and restoration of TRAIL-sensitivity by ciglitazone in resistant cervical cancer cells.Oncotarget · 2017Article
- The exon junction complex senses energetic stress and regulates contractility and cell architecture in cardiac myocytes.Bioscience reports · 2017Article
- Functional activation of PPARγ in human upper aerodigestive cancer cell lines.Molecular carcinogenesis · 2017Article
- Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms.Medical science monitor : international medical journal of experimental and clinical research · 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDoxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. EXPERIMENTAL APPROACH: We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. KEY
resultsDoxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1/S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF-7 cells. CONCLUSIONS AND IMPLICATIONS: Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.
Indexed as
Identifiers
What OpenQuestion holds
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.