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Treatment of a mantle cell lymphoma cell line with cannabinoids and cytostatics: - effects on DNA synthesis and ceramide metabolism
Mälardalen University, School of Sustainable Development of Society and Technology. Mälardalen University, Department of Biology and Chemical Engineering.
2009 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with bad prognosis, which predominates in males with advanced age. However, studies of the endocannabinoid system and how it affects tumour behaviour provides the basis for designing innovative therapeutic strategies that could open new opportunities for treatment of patient with MCL. It has earlier been shown that the cannabinoid receptor ligand (R)-(+)-methanandamide (R-MA) induce cell death in MCL by accumulation of ceramide. Ceramide has a pro-apoptotic effect on the cell but could be metabolized by the enzymes glucosylceramide synthase (GCS) and sphingosine kinase 1 (SphK1) to molecules with pro-proliferative effect. Therefore, treatments with R-MA on Jeko-1 MCL cell line were performed in this study to determine interference in the proliferative behaviour as well as in the gene expression of the enzymes GCS and SphK1. In addition, treatments with chemotherapeutic substances, such as doxorubicin or cytarabine (Ara-C), and combinations of R-MA and chemotherapeutic substance, were performed for the same reason. Results showed that the proliferation behaviour of Jeko cells remained unaffected when treated with R-MA, in contrast to the decreased proliferative effects shown when treated with cytostatics or combinations of R-MA and cytostatics. Furthermore, a tendency for up-regulation of GCS and SphK1 expression was recognized when cells were treated with cytostatics or combination of cytostatics and R-MA, in contrast to cells treated with R-MA alone. Although, R-MA alone had a tendency for a small down-regulation of GCS expression, it contributed to a potential elevation of GCS expression when combined with Ara-C or doxorubicin. It is believed that the effect from upregulated levels of the metabolizing enzymes GCS and SphK1 is balanced by, earlier observed, up-regulations of the ceramide synthesis enzymes.

Place, publisher, year, edition, pages
2009. , 18 p.
Keyword [en]
cancer, mantle cell lymphoma, cannabinoids, cytostatics, ceramide
National Category
Medical and Health Sciences Pharmacology and Toxicology Cell and Molecular Biology Industrial Biotechnology Other Clinical Medicine
Identifiers
URN: urn:nbn:se:mdh:diva-7584OAI: oai:DiVA.org:mdh-7584DiVA: diva2:278662
Presentation
(English)
Uppsok
Physics, Chemistry, Mathematics
Supervisors
Examiners
Available from: 2009-11-30 Created: 2009-11-27 Last updated: 2009-11-30Bibliographically approved

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Chabo, Ablahad
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CiteExportLink to record
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Citation style
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