P62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)-Curcumin Complex
| العنوان: | P62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)-Curcumin Complex |
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| المؤلفون: | Alessia Garufi, Maria Saveria Gilardini Montani, Alessandra Crispini, Mara Cirone, Eugenia Giorno, Gabriella D'Orazi, Giuseppa Pistritto |
| المصدر: | Biomolecules Biomolecules, Vol 11, Iss 348, p 348 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, p53, Programmed cell death, Chromatin Immunoprecipitation, Keap1, Curcumin, Cell Survival, NF-E2-Related Factor 2, p62/SQSTM1, Blotting, Western, lcsh:QR1-502, Biochemistry, environment and public health, lcsh:Microbiology, NRF2, cancer cells, drug sensitivity, keap1, P53, P62/SQSTM1, zinc compounds, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Sequestosome-1 Protein, medicine, Gene silencing, Humans, Molecular Biology, Gene knockdown, Kelch-Like ECH-Associated Protein 1, Cell Death, Reverse Transcriptase Polymerase Chain Reaction, Communication, Cancer, RNA-Binding Proteins, respiratory system, medicine.disease, KEAP1, Crosstalk (biology), 030104 developmental biology, chemistry, Zinc Compounds, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, RNA Interference |
| الوصف: | The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies. |
| تدمد: | 2218-273X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25cad4260d9a92e1a0d67ebb7a224124Test https://pubmed.ncbi.nlm.nih.gov/33669070Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....25cad4260d9a92e1a0d67ebb7a224124 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2218273X |
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