| Full text | |
| Author(s): |
Tortelli, Jr., Tharcisio Citrangulo
[1, 2]
;
Tamura, Rodrigo Esaki
[1, 2, 3]
;
Junqueira, Mara de Souza
[1, 2]
;
Mororo, Janio da Silva
[1, 2]
;
Bustos, Silvina Odete
[1, 2]
;
Natalino, Renato Jose Mendonca
[1, 2]
;
Russell, Shonagh
[4]
;
Desaubry, Laurent
[5]
;
Strauss, Bryan Eric
[1, 2]
;
Chammas, Roger
[1, 2]
Total Authors: 10
|
| Affiliation: | [1] Univ Sao Paulo, Ctr Invest Translac Oncol LIM24, Dept Radiol & Oncol, Fac Med, BR-01246000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Canc Estado Sao Paulo, BR-01246000 Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Lab Canc Mol Biol, BR-04039002 Sao Paulo, SP - Brazil
[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Physiol, Tampa, FL 33612 - USA
[5] Univ Strasbourg, CRBS, Lab Regenerat Nanomed RNM, INSERM, U1260, F-67000 Strasbourg - France
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | AGING-US; v. 13, n. 18, p. 21914-21940, SEP 30 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
Metformin has been tested as an anti-cancer therapy with potential to improve conventional chemotherapy. However, in some cases, metformin fails to sensitize tumors to chemotherapy. Here we test if the presence of P53 could predict the activity of metformin as an adjuvant for cisplatin-based therapy in non-small cell lung cancer (NSCLC). A549, HCC 827 (TP53 WT), H1299, and H358 (TP53 null) cell lines were used in this study. A549 cells were pre-treated with a sub-lethal dose of cisplatin to induce chemoresistance. The effects of metformin were tested both in vitro and in vivo and related to the ability of cells to accumulate Jarid1b, a histone demethylase involved in cisplatin resistance in different cancers. Metformin sensitized A549 and HCC 827 cells (but not H1299 and H358 cells) to cisplatin in a P53-dependent manner, changing its subcellular localization to the mitochondria. Treatment with a sub-lethal dose of cisplatin increased Jarid1b expression, yet downregulated P53 levels, protecting A549Res cells from metformin-induced chemosensitization to cisplatin and favored a glycolytic phenotype. Treatment with FL3, a synthetic flavagline, sensitized A549Res cells to cisplatin. In conclusion, metformin could potentially be used as an adjuvant for cisplatin-based therapy in NSCLC cells if wild type P53 is present. (AU) | |
| FAPESP's process: | 15/26580-9 - Cancer gene therapy: strategic positioning for translational studies |
| Grantee: | Bryan Eric Strauss |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/08147-7 - Analysis of the metabolic profile and mathematical modeling of cisplatin-induced chemoresistant A549 NSCLC cells through Jardi1b overexpression |
| Grantee: | Tharcisio Citrangulo Tortelli Junior |
| Support Opportunities: | Scholarships abroad - Research |
| FAPESP's process: | 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment |
| Grantee: | Carlos Eduardo Negrão |
| Support Opportunities: | Research Projects - Thematic Grants |