Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma
| Autor: | Miguel Gallardo, Alicia Gimenez, Joaquin Martinez-Lopez, Laura Moreno, Santiago Barrio, Pedro Aguilar-Garrido, Carmen Bárcena, María Luz Morales, Rosa Maria Garcia-Martin, Antonio Valeri, Vanesa Garrido, Alejandra Ortiz-Ruiz, Yanira Ruiz-Heredia, Eva Lospitao, Miguel Ángel Navarro-Aguadero, Maria Velasco-Estevez, Almudena García-Ortiz, María Linares, María Teresa Cedena |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Disease MYC Mitochondrion lcsh:RC254-282 Article Oncología Pathogenesis 03 medical and health sciences 0302 clinical medicine In vivo Medicine Hematología Cytotoxicity Multiple myeloma Biología celular business.industry Bortezomib medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens In vitro multiple myeloma mitochondria 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research tigecycline business medicine.drug |
| Zdroj: | Cancers, Vol 13, Iss 1662, p 1662 (2021) Cancers E-Prints Complutense. Archivo Institucional de la UCM instname Volume 13 Issue 7 |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary Multiple myeloma represents the cancer with the 21st highest global incidence. The rapid acquisition of drug resistance to proteasome inhibitors requires a deep knowledge on the mechanisms involved in proliferation in order to provide novel targets for the disease. The aim of our study was to characterize the mitochondrial activity in primary multiple myeloma (MM) cells along the course of the disease and to provide a therapeutic alternative to inhibit Myc function by blocking OXPHOS metabolism. We confirmed MM patients show enhanced mitochondrial activity linked to c-Myc expression. The use of tigecycline provides evidence for a novel strategy addressing c-Myc functionality by mitochondrial activity inhibition. Abstract Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities. |
| Databáze: | OpenAIRE |
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