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Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antit...

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Autores principales: Cacciola, Nunzio Antonio, Salzano, Angela, D’Onofrio, Nunzia, Venneri, Tommaso, Cicco, Paola De, Vinale, Francesco, Petillo, Orsolina, Martano, Manuela, Maiolino, Paola, Neglia, Gianluca, Campanile, Ciro, Severino, Lorella, Merola, Carmine, Borrelli, Francesca, Balestrieri, Maria Luisa, Campanile, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368892/
https://www.ncbi.nlm.nih.gov/pubmed/35955595
http://dx.doi.org/10.3390/ijms23158464
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author Cacciola, Nunzio Antonio
Salzano, Angela
D’Onofrio, Nunzia
Venneri, Tommaso
Cicco, Paola De
Vinale, Francesco
Petillo, Orsolina
Martano, Manuela
Maiolino, Paola
Neglia, Gianluca
Campanile, Ciro
Severino, Lorella
Merola, Carmine
Borrelli, Francesca
Balestrieri, Maria Luisa
Campanile, Giuseppe
author_facet Cacciola, Nunzio Antonio
Salzano, Angela
D’Onofrio, Nunzia
Venneri, Tommaso
Cicco, Paola De
Vinale, Francesco
Petillo, Orsolina
Martano, Manuela
Maiolino, Paola
Neglia, Gianluca
Campanile, Ciro
Severino, Lorella
Merola, Carmine
Borrelli, Francesca
Balestrieri, Maria Luisa
Campanile, Giuseppe
author_sort Cacciola, Nunzio Antonio
collection PubMed
description Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.
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spelling pubmed-93688922022-08-12 Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer Cacciola, Nunzio Antonio Salzano, Angela D’Onofrio, Nunzia Venneri, Tommaso Cicco, Paola De Vinale, Francesco Petillo, Orsolina Martano, Manuela Maiolino, Paola Neglia, Gianluca Campanile, Ciro Severino, Lorella Merola, Carmine Borrelli, Francesca Balestrieri, Maria Luisa Campanile, Giuseppe Int J Mol Sci Article Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC. MDPI 2022-07-30 /pmc/articles/PMC9368892/ /pubmed/35955595 http://dx.doi.org/10.3390/ijms23158464 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cacciola, Nunzio Antonio
Salzano, Angela
D’Onofrio, Nunzia
Venneri, Tommaso
Cicco, Paola De
Vinale, Francesco
Petillo, Orsolina
Martano, Manuela
Maiolino, Paola
Neglia, Gianluca
Campanile, Ciro
Severino, Lorella
Merola, Carmine
Borrelli, Francesca
Balestrieri, Maria Luisa
Campanile, Giuseppe
Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title_full Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title_fullStr Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title_full_unstemmed Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title_short Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer
title_sort buffalo milk whey activates necroptosis and apoptosis in a xenograft model of colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368892/
https://www.ncbi.nlm.nih.gov/pubmed/35955595
http://dx.doi.org/10.3390/ijms23158464
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