IMMUNEPOTENT CRP induces cell cycle arrest and caspase-independent regulated cell death in HeLa cells through reactive oxygen species production
| Autor: | Milena Benítez-Londoño, Alejandra Reyes-Ruiz, Cristina Rodríguez-Padilla, Ana Carolina Martínez-Torres, Moisés Armides Franco-Molina |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cell Extracts
0301 basic medicine Cell death Cancer Research Programmed cell death Cell cycle checkpoint Cell Uterine Cervical Neoplasms Antineoplastic Agents Apoptosis lcsh:RC254-282 HeLa 03 medical and health sciences Bovine dyalisable leukocyte extract Transfer factor Genetics medicine Animals Humans Viability assay bDLE I-CRP Caspase Membrane Potential Mitochondrial biology Chemistry Cell Cycle Checkpoints Cell cycle biology.organism_classification lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Mitochondria Cell biology C-Reactive Protein 030104 developmental biology medicine.anatomical_structure Oncology Caspases biology.protein Cervical cancer Cattle Female Immunomodulator Immunotherapy Reactive Oxygen Species HeLa Cells Research Article |
| Zdroj: | BMC Cancer, Vol 18, Iss 1, Pp 1-13 (2018) BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background Regulated cell death (RCD) is a mechanism by which the cell activates its own machinery to self-destruct. RCD is important for the maintenance of tissue homeostasis and its deregulation is involved in diseases such as cervical cancer. IMMUNEPOTENT CRP (I-CRP) is a dialyzable bovine leukocyte extract that contains transfer factors and acts as an immunomodulator, and can be cytotoxic to cancer cell lines and reduce tumor burden in vivo. Although I-CRP has shown to improve or modulate immune response in inflammation, infectious diseases and cancer, its widespread use has been limited by the absence of conclusive data on the molecular mechanism of its action. Methods In this study we analyzed the mechanism by which I-CRP induces cytotoxicity in HeLa cells. We assessed cell viability, cell death, cell cycle, nuclear morphology and DNA integrity, caspase dependence and activity, mitochondrial membrane potential, and reactive oxygen species production. Results I-CRP diminishes cell viability in HeLa cells through a RCD pathway and induces cell cycle arrest in the G2/M phase. We show that the I-CRP induces caspase activation but cell death induction is independent of caspases, as observed by the use of a pan-caspase inhibitor, which blocked caspase activity but not cell death. Moreover, we show that I-CRP induces DNA alterations, loss of mitochondrial membrane potential, and production of reactive-oxygen species. Finally, pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation and cell death induced by I-CRP. Conclusions Our data indicate that I-CRP treatment induced cell cycle arrest in G2/M phase, mitochondrial damage, and ROS-mediated caspase-independent cell death in HeLa cells. This work opens the way to the elucidation of a more detailed cell death pathway that could potentially work in conjunction with caspase-dependent cell death induced by classical chemotherapies. Electronic supplementary material The online version of this article (10.1186/s12885-017-3954-5) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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