ArticleCancer immunology, immunotherapy : CII2016
Phloretin increases the anti-tumor efficacy of intratumorally delivered heat-shock protein 70 kDa (HSP70) in a murine model of melanoma.
Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- New Strategies in Comprehensive Melanoma Treatment: Applications, Potential, and Challenges of Hydrogels.International journal of nanomedicine · 2025Pooled it
- A new look at Hsp70 activity in phosphatidylserine-enriched membranes: chaperone-induced quasi-interdigitated lipid phase.Scientific reports · 2023Article
- Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions.Molecules (Basel, Switzerland) · 2022Review
- Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin.Nutrients · 2022Review
- Hsp70-containing extracellular vesicles are capable of activating of adaptive immunity in models of mouse melanoma and colon carcinoma.Scientific reports · 2021Article
- Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Review
- Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets.Cells · 2020Review
- Phloretin Modulates Human Th17/Treg Cell Differentiation In Vitro via AMPK Signaling.BioMed research international · 2020Article
- Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells.International journal of molecular sciences · 2019Article
- Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1-mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma.Cell communication and signaling : CCS · 2019Article
- Biochemical Basis of Anti-Cancer-Effects of Phloretin-A Natural Dihydrochalcone.Molecules (Basel, Switzerland) · 2019Review
- Heat Shock Proteins in Cancer Immunotherapy.Journal of oncology · 2019Review
- Sensitizing tumor cells to conventional drugs: HSP70 chaperone inhibitors, their selection and application in cancer models.Cell death & disease · 2018Article
- Purification and characterization of a novel phloretin-2'-O-glycosyltransferase favoring phloridzin biosynthesis.Scientific reports · 2016Article
- HSP70-based anti-cancer immunotherapy.Human vaccines & immunotherapeutics · 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
No grant is acknowledged in the PubMed record.
Abstract
Recombinant HSP70 chaperone exerts a profound anticancer effect when administered intratumorally. This action is based on the ability of HSP70 to penetrate tumor cells and extract its endogenous homolog. To enhance the efficacy of HSP70 cycling, we employed phloretin, a flavonoid that enhances the pore-forming activity of the chaperone on artificial membranes. Phloretin increased the efficacy of HSP70 penetration in B16 mouse melanoma cells and K-562 human erythroblasts; this was accompanied with increased transport of the endogenous HSP70 to the plasma membrane. Importantly, treatment with HSP70 combined with phloretin led to the elevation of cell sensitivity to cytotoxic lymphocytes by 16-18 % compared to treatment with the chaperone alone. The incubation of K-562 cells with biotinylated HSP70 and phloretin increased the amount of the chaperone released from cells, suggesting that chaperone cycling could trigger a specific anti-tumor response. We studied the effect of the combination of HSP70 and phloretin using B16 melanoma and a novel method of HSP70-gel application. We found that the addition of phloretin to the gel reduced tumor weight almost fivefold compared with untreated mice, while the life span of the animals extended from 25 to 39 days. The increased survival was corroborated by the activation of innate and adaptive immunity; interestingly, HSP70 was more active in induction of CD8+ cell-mediated toxicity and γIFN production while phloretin contributed largely to the CD56+ cell response. In conclusion, the combination of HSP70 with phloretin could be a novel treatment for efficient immunotherapy of intractable cancers such as skin melanoma.
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.