Abstract
BackgroundDiet and obesity are recognized in the scientific literature as important risk factors for cancer development and progression. Hypercholesterolemia facilitates lymphoma lymphoblastic cell growth and in time turns in hypocholesterolemia that is a sign of tumour progression. The present study examined how and where the cholesterol acts in cancer cells when you reproduce in vitro an in vivo hypercholesterolemia condition.MethodsWe used non-Hodgkin’s T cell human lymphoblastic lymphoma (SUP-T1 cell line) and we studied cell morphology, aggressiveness, gene expression for antioxidant proteins, polynucleotide kinase/phosphatase and actin, cholesterol and sphingomyelin content and finally sphingomyelinase activity in whole cells, nuclei and nuclear lipid microdomains.ResultsWe found that cholesterol changes cancer cell morphology with the appearance of protrusions together to the down expression of β-actin gene and reduction of β-actin protein. The lipid influences SUP-T1 cell aggressiveness since stimulates DNA and RNA synthesis for cell proliferation and increases raf1 and E-cadherin, molecules involved in invasion and migration of cancer cells. Cholesterol does not change GRX2 expression but it overexpresses SOD1, SOD2, CCS, PRDX1, GSR, GSS, CAT and PNKP. We suggest that cholesterol reaches the nucleus and increases the nuclear lipid microdomains known to act as platform for chromatin anchoring and gene expression.ConclusionThe results imply that, in hypercholesterolemia conditions, cholesterol reaches the nuclear lipid microdomains where activates gene expression coding for antioxidant proteins. We propose the cholesterolemia as useful parameter to monitor in patients with cancer.
Highlights
Diet and obesity are recognized in the scientific literature as important risk factors for cancer development and progression
We previously demonstrated the presence of lipid microdomains (LMs) in the nucleus, in association with inner nuclear membrane (Nuclear Lipid Microdomains, NLMs), where they acted as platform for active chromatin anchoring, DNA duplication and transcription process [12, 13]
How the high level of cholesterol influences lymphoblastic lymphoma cells We have previously demonstrated that by enriching the culture medium with 800 nM CHO you reached a level of CHO corresponding to hyperCHO (280 mg/dl in the blood of patients)
Summary
Diet and obesity are recognized in the scientific literature as important risk factors for cancer development and progression. Hypercholesterolemia facilitates lymphoma lymphoblastic cell growth and in time turns in hypocholesterolemia that is a sign of tumour progression. Cholesterol (CHO)-rich diet is considered an important risk factor for cancer development [1,2,3]. In vitro, when serum CHO concentration was 800 nM corresponding to 280 mg/dl in the blood of patients, non-Hodgkin’s T cell human lymphoblastic lymphoma cells (SUP-T1) incorporated CHO with avidity and used it for their proliferation [6]. Normal CHO concentration did not influence tumour growth; otherwise hyperCHO facilitated the entry of CHO into the cells by stimulating cell growth and Codini et al Lipids in Health and Disease (2016) 15:4 inducing severe hypoCHO [6]. After cell treatment with CHO disrupting or usurping agents, raftassociated proteins and lipids were dissociated and disease severity was mitigated [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
