Synergistic promoting effects of pentoxifylline and simvastatin on the apoptosis of triple-negative MDA-MB-231 breast cancer cells
| Autor: | Rémi Varin, Yessica Cristina Castellanos-Esparza, Hong Li, Anne Janin, He Lu, Berenice Sanchez-Gonzalez, Rong Shen, Limin Huang, Jean-Pierre Vannier, Olivier Boyer, Catherine Buquet, Ethel Awilda García Latorre, Shuang Wu, Jiménez-Zamudio L |
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| Přispěvatelé: | Zhejiang University, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Pharmacie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hemostase, Endothelium, Angiogenese (UMR_S_553) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Simvastatin Cancer Research [SDV]Life Sciences [q-bio] Apoptosis Triple Negative Breast Neoplasms [SDV.CAN]Life Sciences [q-bio]/Cancer Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Autophagy Humans Propidium iodide Pentoxifylline Clonogenic assay PI3K/AKT/mTOR pathway ComputingMilieux_MISCELLANEOUS Cell Proliferation Cell growth Drug Synergism Cell cycle 3. Good health 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer cell Cancer research Female |
| Zdroj: | International Journal of Oncology International Journal of Oncology, Spandidos Publications, 2018, ⟨10.3892/ijo.2018.4272⟩ |
| ISSN: | 1019-6439 1791-2423 |
| Popis: | Pentoxifylline (PTX), a xanthine family molecule and simvastatin (SIM), an anti-hypercholesterolemic agent, have recently been considered as sensitizers to chemotherapy and radiotherapy. The present in vitro study evaluated their antitumor synergistic effects on MDA‑MB‑231 breast cancer cells characterized by the triple‑negative phenotype (TNP). The anti-proliferative effects of these two agents were evaluated by MTT and clonogenic assays. Cell cycle progression was examined using propidium iodide staining. Apoptosis was investigated by Annexin V labeling, and by examining caspase 3 activity and DNA fragmentation. Autophagic vesicles and reactive oxygen species (ROS) levels were monitored by flow cytometry. Western blot analysis was performed to evaluate molecular targets. Our results revealed that when used alone, PTX and SIM exerted antitumor effects. Nevertheless, used in combination, the inhibition of cell proliferation was synergistically superior (80% vs 42%) than that observed following treatment with each agent alone after 48 h. PTX alone (0.5 mM) induced both apoptosis (25%) and autophagy (25%); however, when used in combination with SIM (0.5 µM), the balance between these processes was disrupted and the cells underwent apoptosis (>65%) as opposed to autophagy ( |
| Databáze: | OpenAIRE |
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