ArticleCancer biology & therapy2015
Antagonistic effects of chloroquine on autophagy occurrence potentiate the anticancer effects of everolimus on renal cancer cells.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Clomipramine potentiates sorafenib efficacy in experimental hepatocellular carcinoma by targeting lysosomal sequestration and modulating the cathepsin B/Bcl-2/Beclin-1 axis.Molecular biology reports · 2026Article
- Simultaneous activation and late-stage inhibition of autophagy induces autophagy-dependent cell death in leukemia.BMC cancer · 2026Article
- Captivating Synergistic, Dose-Dependent Anticancer Effects of Tumor-Regulation Modulators Chloroquine and Ivermectin Completely Abolished by an Opposing Modulator, Deoxycholic Acid, in Hamster Fibrosarcoma: In Vivo, In Vitro, and Literature Review.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Treatment of Melanoma Cells with Chloroquine and Everolimus Activates the Apoptosis Process and Alters Lipid Redistribution.International journal of molecular sciences · 2024Article
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment.International journal of molecular sciences · 2024Review
- Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470 Synergistically Inhibit Renal Cell Carcinoma Pathogenesis.Journal of Cancer · 2024Article
- The Molecular Mechanism and Therapeutic Application of Autophagy for Urological Disease.International journal of molecular sciences · 2023Review
- Isoginkgetin, a potential CDK6 inhibitor, suppressesAutophagy · 2023Article
- Article
- Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling.Annals of translational medicine · 2021Article
- Article
- H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets.Oxidative medicine and cellular longevity · 2021Article
- Review
- Targeting Autophagy in Breast Cancer.International journal of molecular sciences · 2020Review
- Chloroquine against malaria, cancers and viral diseases.Drug discovery today · 2020Review
- The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?Nutrients · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma is an aggressive disease often asymptomatic and weakly chemo-radiosensitive. Currently, new biologic drugs are used among which everolimus, an mTOR inhibitor, that has been approved for second-line therapy. Since mTOR is involved in the control of autophagy, its antitumor capacity is often limited. In this view, chloroquine, a 4-alkylamino substituted quinoline family member, is an autophagy inhibitor that blocks the fusion of autophagosomes and lysosomes. In the present study, we evaluated the effects of everolimus alone or in combination with chloroquine on renal cancer cell viability and verified possible synergism. Our results demonstrate that renal cancer cells are differently sensitive to everolimus and chloroquine and the pharmacological combination everolimus/chloroquine was strongly synergistic inducing cell viability inhibition. In details, the pharmacological synergism occurs when chloroquine is administered before everolimus. In addition, we found a flow autophagic block and shift of death mechanisms to apoptosis. This event was associated with decrease of Beclin-1/Bcl(-)2 complex and parallel reduction of anti-apoptotic protein Bcl(-)2 in combined treatment. At last, we found that the enhancement of apoptosis induced by drug combination occurs through the intrinsic mitochondrial apoptotic pathway activation, while the extrinsic pathway is involved only partly following its activation by chloroquine. These results provide the basis for new therapeutic strategies for the treatment of renal cell carcinoma after appropriate clinical trial.
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