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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2014

01-10-2014 | Original Article

Resistance to the antiproliferative effect induced by a short-chain ceramide is associated with an increase of glucosylceramide synthase, P-glycoprotein, and multidrug-resistance gene-1 in cervical cancer cells

Authors: Gisela Gutiérrez-Iglesias, Yamilec Hurtado, Icela Palma-Lara, Rebeca López-Marure

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2014

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Abstract

Purpose

Ceramide is glycosylated to glucosylceramide or lactosylceramide, and this glycosylation is a novel multidrug-resistance (MDR) mechanism. In this work, a short-chain ceramide (C6), lactosylceramide (LacCer), and an inhibitor of ceramide glycosylation (d-threo-1-phenyl-2-decanoylamino-3-1-propanol, PDMP) were evaluated on the proliferation of cervical cancer cells. The participation of glucosylceramide synthase (GCS), P-glycoprotein (P-gp), and multidrug-resistance gene-1 (MDR-1) in the resistance to the antiproliferative effect induced by C6 was also evaluated.

Methods

Cell proliferation was determined by crystal violet staining. GCS and MDR-1 mRNA expression was evaluated by real-time RT-PCR assay. GCS and P-gp protein expressions, as well as Rhodamine 123 uptake, which is a functional test for P-gp efflux activity, were determined by flow cytometry.

Results

C6 inhibited proliferation of CaLo and CasKi cells with an IC50 of 2.5 μM; however, 50 % proliferation of ViBo cells was inhibited with 10 μM. LacCer increased the proliferation of all cells. When cells were treated with PDMP plus C6, no additional effect on antiproliferation induced by C6 was observed in CaLo and CasKi cells; however, proliferation diminished in comparison with C6 alone in ViBo cells. C6 increased GCS and MDR-1 expression in all cells, as well as P-gp expression in CasKi cells.

Conclusions

Cells that have more capacity to glycosylate ceramide and express a higher level of GCS, MDR-1, and P-gp, are more resistant to the antiproliferative effect induced by C6.
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Metadata
Title
Resistance to the antiproliferative effect induced by a short-chain ceramide is associated with an increase of glucosylceramide synthase, P-glycoprotein, and multidrug-resistance gene-1 in cervical cancer cells
Authors
Gisela Gutiérrez-Iglesias
Yamilec Hurtado
Icela Palma-Lara
Rebeca López-Marure
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2552-3

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