ArticleJournal of cellular and molecular medicine
Synergistic promotion of breast cancer cells death by targeting molecular chaperone GRP78 and heat shock protein 70.
Article in Journal of cellular and molecular medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Epigallocatechin-3-gallate as a hepatoprotective agent against ochratoxin a: modulating ER stress and NF-κB/TNF-α/IL-6 responses.Mycotoxin research · 2026Article
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multifaceted Anticancer Activity of Flavanone/Chromanone Intermediates for Five-Membered Heterocyclic Derivatives: Targeting Oxidative Stress, Apoptosis, and MAPK Signaling in Colorectal Cancer.Molecules (Basel, Switzerland) · 2026Article
- Synergistic targeting of cancer-related proteins by benzyl isothiocyanate and caffeic acid: MLSD and cytotoxic mechanisms in MCF-7 cells.3 Biotech · 2025Article
- Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients.The EPMA journal · 2025Article
- The abrogation of GRP78 sensitizes liver cancer cells to lysionotin by enhancing ER stress-mediated pro-apoptotic pathway.Cell stress & chaperones · 2023Article
- Review
- Advances in the study of HSP70 inhibitors to enhance the sensitivity of tumor cells to radiotherapy.Frontiers in cell and developmental biology · 2022Review
- Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer.Frontiers in pharmacology · 2022Review
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers.Oncogenesis · 2017Review
- Targeting Hsp70: A possible therapy for cancer.Cancer letters · 2016Review
- Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma.Oncotarget · 2015Article
- Green tea compounds in breast cancer prevention and treatment.World journal of clinical oncology · 2014Review
- JNK contributes to the tumorigenic potential of human cholangiocarcinoma cells through the mTOR pathway regulated GRP78 induction.PloS one · 2014Article
- Inhibition of established micrometastases by targeted drug delivery via cell surface-associated GRP78.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies.Oncogene · 2013Review
- Phage display biopanning identifies the translation initiation and elongation factors (IF1α-3 and eIF-3) as components of Hsp70-peptide complexes in breast tumour cells.Cell stress & chaperones · 2012Article
- The anticancer flavonoid chrysin induces the unfolded protein response in hepatoma cells.Journal of cellular and molecular medicine · 2011Article
- Pseudomonas aeruginosa exotoxin A reduces chemoresistance of oral squamous carcinoma cell via inhibition of heat shock proteins 70 (HSP70).Yonsei medical journal · 2010Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 70 (HSP70) is frequently overexpressed in a variety of human malignancies and protects cancer cells against apoptosis in response to various stresses. The bioflavonoid quercetin inhibits HSP70 expression and induces cancer cells apoptosis. In the present study, we have investigated the effects of HSP70 down-regulation on the unfolded protein response (UPR) and addressed a novel strategy to enhance the proapoptotic effect of quercetin by suppressing GRP78 induction simultaneously. Treatment of human breast cancer cells with quercetin down-regulates HSP70 expression, but up-regulates GRP78 expression in a dose-dependent manner. Down-regulation of HSP70 by small interfering RNA also leads to induction of GRP78. Moreover, our studies reveal that HSP70 knockdown or quercetin induces other typical components of the UPR, including CHOP expression, eIF2alpha and JNK phosphorylation, caspases activation and XBP-1 splicing. Abrogating the induction of pro-survival chaperone GRP78 by small interfering RNA sensitizes breast cancer cells to quercetin. Colony survival assays demonstrate that treatment of breast cancer cells with green tea (-)-epigallocatechin gallate (EGCG), which binds to the ATP-binding domain of GRP78 and blocks its protective function, synergistically promoted quercetin-induced cell death. These studies reveal that HSP70 down-regulation leads to the induction of UPR. The pro-survival GRP78 induction contributes to quercetin resistance. Abrogation of GRP78 induction or inhibition of GRP78 activity increases the effectiveness of quercetin. These findings indicate that combinational administration of flavonoids capable of suppressing HSP70 and GRP78 such as quercetin and EGCG might represent a novel approach for cancer therapy or chemoprevention.
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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.