Format

Send to

Choose Destination
J Dairy Sci. 2018 Jun;101(6):4853-4863. doi: 10.3168/jds.2017-13731. Epub 2018 Mar 15.

α-Lactalbumin-oleic acid complex kills tumor cells by inducing excess energy metabolism but inhibiting mRNA expression of the related enzymes.

Author information

1
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address: bingfang@cau.edu.cn.
2
School of Food Science and Chemical Engineering, Beijing Technology and Business University, Beijing 100048, China.
3
Key Laboratory of Functional Dairy, co-constructed by Ministry of Education and Beijing Government, and Beijing Laboratory of Food Quality and Safety, China Agricultural University, Beijing 100083, China.
4
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
5
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Functional Dairy, co-constructed by Ministry of Education and Beijing Government, and Beijing Laboratory of Food Quality and Safety, China Agricultural University, Beijing 100083, China.

Abstract

Previous studies have demonstrated that the anti-tumor α-lactalbumin-oleic acid complex (α-LA-OA) may target the glycolysis of tumor cells. However, few data are available regarding the effects of α-LA-OA on energy metabolism. In this study, we measured glycolysis and mitochondrial functions in HeLa cells in response to α-LA-OA using the XF flux analyzer (Seahorse Bioscience, North Billerica, MA). The gene expression of enzymes involved in glycolysis, tricarboxylic acid cycle, electron transfer chain, and ATP synthesis were also evaluated. Our results show that α-LA-OA significantly enhanced the basal glycolysis and glycolytic capacity. Mitochondrial oxidative phosphorylation, including the basal respiration, maximal respiration, spare respiratory capacity and ATP production were also improved in response to α-LA-OA. The enhanced mitochondrial functions maybe partly due to the increased capacity of utilizing fatty acids and glutamine as the substrate. However, the gene expressions of pyruvate kinase M2, lactate dehydrogenase A, aconitate hydratase, and isocitrate dehydrogenase 1 were inhibited, suggesting an insufficient ability for the glycolysis process and the tricarboxylic acid cycle. The increased expression of acetyl-coenzyme A acyltransferase 2, a central enzyme involved in the β-oxidation of fatty acids, would enhance the unbalance due to the decreased expression of electron transfer flavoprotein β subunit, which acts as the electron acceptor. These results indicated that α-LA-OA may induce oxidative stress due to conditions in which the ATP production is exceeding the energy demand. Our results may help clarify the mechanism of apoptosis induced by reactive oxygen species and mitochondrial destruction.

KEYWORDS:

extracellular acidification rate; glycolysis; mitochondrial oxidative phosphorylation; oxygen consumption rate; tricarboxylic acid cycle

PMID:
29550120
DOI:
10.3168/jds.2017-13731
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center