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Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells
- Source :
- Oncology Reports, Oncology Reports, Spandidos Publications, 2017, 38 (5), pp.3254-3264. ⟨10.3892/or.2017.6009⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS production in patho-logical processes such as cancer. NOX-driven ROS production is involved in cell mechanisms from signalling to oxidative stress. Leptin, an adipokine overexpressed in obese patients, has been investigated in studies on breast carcinogenesis, but its effects on oxidative stress remain largely unexplored, especially in breast cancer. The study used three human mammary epithelial cell models presenting different neoplastic status (healthy primary HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the effects of leptin on short-term ROS production and to characterize the enzymes involved. All three cell models significantly expressed NADPH oxidase isoform 5 (NOX5) in our culture conditions. All models showed induced ROS production regardless of leptin concentration (10 ng/ml mimicking good health, 100 ng/ml mimicking obesity). Cell treatment with either siRNA against NOX5, NOX inhibitor DPI or a calcium channel blocker (verapamil) confirmed the putative involvement of the NOX5 isoenzyme in ROS production. Moreover, cell treatments suppressed ROS production under leptin at both concentrations. Neoplastic cells appeared unable to downregulate NOX5 mRNA expression under leptin. Leptin emerged as a potential activator of ROS production in human epithelial mammary cells, where the ROS production was apparently linked to NOX5 activation. This novel finding could shed light on the potential role of obesity-associated hyperleptinemia in mammary cells via the activation of NOX enzymes.
- Subjects :
- 0301 basic medicine
Leptin
Cancer Research
Cell
Adipokine
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
medicine
Humans
cancer
cellule épithéliale mammaire
RNA, Small Interfering
Mammary Glands, Human
patient obèse
NADPH oxidase
Epithelial Cells
ROS
General Medicine
Cell cycle
stress oxydant
Gene Expression Regulation, Neoplastic
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Oncology
NADPH Oxidase 5
Verapamil
Apoptosis
030220 oncology & carcinogenesis
biology.protein
Cancer research
MCF-7 Cells
Female
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Reactive Oxygen Species
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 1021335X
- Database :
- OpenAIRE
- Journal :
- Oncology Reports, Oncology Reports, Spandidos Publications, 2017, 38 (5), pp.3254-3264. ⟨10.3892/or.2017.6009⟩
- Accession number :
- edsair.doi.dedup.....10b8491b5dce942b16b0285d51d46994