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  2. Ceramide promotes the death of human cervical tumor cells in the absence of biochemical and morphological markers of apoptosis

Ceramide promotes the death of human cervical tumor cells in the absence of biochemical and morphological markers of apoptosis

  • Biochem Biophys Res Commun. 2002 May 10;293(3):1028-36. doi: 10.1016/S0006-291X(02)00315-7.
Rebeca López-Marure 1 Gisela Gutiérrez Criselda Mendoza José Luis Ventura Luis Sánchez Elba Reyes Maldonado Alejandro Zentella Luis Felipe Montaño
Affiliations

Affiliation

  • 1 Departamento de Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Colonia Sección 16, Tlalpan, C.P. 14080, Mexico DF, Mexico. rmarure@hotmail.com
Abstract

C8-ceramide, a synthetic cell-permeable analog of endogenous ceramides, interfered with cell proliferation, and was cytotoxic to papilloma virus-containing human cervix carcinoma cells, CALO, INBL, and HeLa, that match two clinical stages of tumor progression. C8-ceramide (3 microM) markedly reduced the tumor cell number after 48 h of treatment, an effect that endured even after the removal of C8-ceramide. The carcinoma cells showed morphologic changes, characteristic of necrosis and released Lactate Dehydrogenase (LDH). A biologically inactive analog C8-dihydro-ceramide had no effect on cell viability in any of the cell lines tested. Seventy-two hours after C8-ceramide treatment none of the biochemical and morphological markers characteristic of apoptosis: (a) nuclear chromatin condensation, (b) DNA fragmentation, (c) proteolysis of the Caspase-3 substrate poly-(ADP-ribose)-polymerase (PARP), and (d) appearance of phosphatidylserine on the external cell membrane, were observed. C8-ceramide had no effect on human cervix fibroblasts and induced a mild reduction (30%) in the proliferation of normal human cervix epithelia and HeLa cells (IV-B metastatic stage). The cytotoxicity of C8-ceramide was restricted to CALO (early II-B) and INBL (IV-A non-metastatic) carcinoma cells. The possible application of ceramide in the treatment of early stages of cervical Cancer is discussed.

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