The novel therapeutic potential of bovine α-lactalbumin made lethal to tumour cells (BALMET) and oleic acid in oral squamous cell carcinoma (OSCC)
| Autor: | Isabel O'Grady, Níal P. Harte, Ken Hun Mok, Nicoleta Sinevici, Soyoung Min, Yongjing Xie, Jeff O'Sullivan |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Programmed cell death Cell cycle checkpoint Epidemiology Antineoplastic Agents Apoptosis medicine.disease_cause Flow cytometry 03 medical and health sciences 0302 clinical medicine medicine Cytotoxic T cell Animals Humans 030212 general & internal medicine Viability assay Cytotoxicity medicine.diagnostic_test Chemistry Squamous Cell Carcinoma of Head and Neck Public Health Environmental and Occupational Health Oncology Cell culture Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Carcinoma Squamous Cell Lactalbumin Cattle Mouth Neoplasms Tumor Suppressor Protein p53 Carcinogenesis Oleic Acid |
| Zdroj: | European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 30(2) |
| ISSN: | 1473-5709 |
| Popis: | Background Since the serendipitous discovery of bovine α-lactalbumin made lethal to tumour cells (BAMLET)/human α-lactalbumin made lethal to tumour cells there has been an increased interest in the ability of the two components, oleic acid and α-lactalbumin, to form anti-cancer complexes. Here we have investigated the in-vitro efficacy of the BAMLET complex in killing oral cancer (OC) cells, determined the active component of the complex and investigated possible biological mechanisms. Materials and methods Two OC cell lines (±p53 mutation) and one dysplastic cell line were used as a model of progressive oral carcinogenesis. We performed cell viability assays with increasing BAMLET concentrations to determine the cytotoxic potential of the complex. We further analysed the individual components to determine their respective cytotoxicities. siRNA knockdown of p53 was used to determine its functional role in mediating sensitivity to BAMLET. Cell death mechanisms were investigated by flow cytometry, confocal microscopy and the lactate dehydrogenase assay. Results Our results show that BAMLET is cytotoxic to the OC and dysplastic cell lines in a time and dose-dependent manner. The cytotoxic component was found to be oleic acid, which, can induce cytotoxicity even when not in complex. Our results indicate that the mechanism of cytotoxicity occurs through multiple simultaneous events including cell cycle arrest, autophagy like processes with a minor involvement of necrosis. Conclusion Deciphering the mechanism of cytotoxicity will aid treatment modalities for OC. This study highlights the potential of BAMLET as a novel therapeutic strategy in oral dysplastic and cancerous cells. |
| Databáze: | OpenAIRE |
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