ArticleInternational journal of cancer2015
Guggulsterone and bexarotene induce secretion of exosome-associated breast cancer resistance protein and reduce doxorubicin resistance in MDA-MB-231 cells.
Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Machine learning-based analysis of cancer cell-derived vesicular proteins revealed significant tumor-specificity and predictive potential of extracellular vesicles for cell invasion and proliferation - A meta-analysis.Cell communication and signaling : CCS · 2023Pooled it
- Phenotypic modulation of corpus cavernosum smooth muscle cells in type 2 diabetic rats is mediated by regulated exosomes secretion via neutral sphingomyelinase-2.Asian journal of andrology · 2026Article
- Breast cancer cell-derived extracellular vesicles accelerate collagen fibrillogenesis and integrate into the matrix.Materials today. Bio · 2026Article
- Lipid metabolism involved in progression and drug resistance of breast cancer.Genes & diseases · 2025Review
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- Exosome-Mediated Cellular Communication in the Tumor Microenvironment Imparts Drug Resistance in Breast Cancer.Cancers · 2025Review
- Extracellular Vesicles as Mediators and Potential Targets in Combating Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2025Review
- The Role of Exosomes as a Key Factor of Cytostatic Resistance in Cancer: Mechanisms of Action, Potential Biomarkers, and Possible Exosome-Based Therapies.Oncology research · 2025Review
- A Narrative Overview of Retinoid X Receptor Inhibitors in Chronic Disease Management.Current drug research reviews · 2025Review
- The Role of The Xihuang Pill in Inhibiting Triple-Negative Breast Cancer Through Immunogenic Cell Death.Breast cancer (Dove Medical Press) · 2025Review
- Synergistic Activation of VDR-RXR Heterodimers by Vitamin D and Rexinoids in Human Kidney and Brain Cells.Cells · 2024Article
- Extracellular Vesicle Mobility in Collagen I Hydrogels Is Influenced by Matrix-Binding Integrins.ACS nano · 2024Article
- Extracellular Vesicles as Surrogates for the Regulation of the Drug Transporters ABCC2 (MRP2) and ABCG2 (BCRP).International journal of molecular sciences · 2024Article
- Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.Life (Basel, Switzerland) · 2023Review
- Exposure to anticancer drugs modulates the expression of ACSL4 and ABCG2 proteins in adrenocortical carcinoma cells.Heliyon · 2023Article
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?Life (Basel, Switzerland) · 2023Review
- Baicalein sensitizes triple negative breast cancer MDA-MB-231 cells to doxorubicin via autophagy-mediated down-regulation of CDK1.Molecular and cellular biochemistry · 2023Article
- MicroRNAs as the critical regulators of autophagy-mediated cisplatin response in tumor cells.Cancer cell international · 2023Review
- Research progress of exosomes in drug resistance of breast cancer.Frontiers in bioengineering and biotechnology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Many breast cancer cells acquire multidrug resistance (MDR) mediated by ABC transporters such as breast cancer resistance protein (BCRP/ABCG2). Here we show that incubation of human breast cancer MDA-MB-231 cells with farnesoid X receptor antagonist guggulsterone (gug) and retinoid X receptor agonist bexarotene (bex) elevated ceramide, a sphingolipid known to induce exosome secretion. The gug+bex combination reduced cellular levels of BCRP to 20% of control cells by inducing its association and secretion with exosomes. Exogenous C6 ceramide also induced secretion of BCRP-associated exosomes, while siRNA-mediated knockdown or GW4869-mediated inhibition of neutral sphingomyelinase 2 (nSMase2), an enzyme generating ceramide, restored cellular BCRP. Immunocytochemistry showed that ceramide elevation and concurrent loss of cellular BCRP was prominent in Aldefluor-labeled breast cancer stem-like cells. These cells no longer excluded the BCRP substrate Hoechst 33342 and showed caspase activation and apoptosis induction. Consistent with reduced BCRP, ABC transporter assays showed that gug+bex increased doxorubicin retention and that the combination of gug+bex with doxorubicin enhanced cell death by more than fivefold. Taken together, our results suggest a novel mechanism by which ceramide induces BCRP secretion and reduces MDR, which may be useful as adjuvant drug treatment for sensitizing breast cancer cells and cancer stem cells to chemotherapy.
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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.