2007
DOI: 10.1158/1535-7163.mct-06-0558
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Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas

Abstract: In this study, quantitative isobologram studies showed that treatment with gemcitabine and doxorubicin, known inducers of ceramide generation, in combination, supraadditively inhibited the growth of human UM-SCC-22A cells in situ. Then, possible involvement of the human homologue of yeast longevity assurance gene 1 (LASS1)/ C 18 -ceramide in chemotherapy-induced cell death in these cells was examined. Gemcitabine/doxorubicin combination treatment resulted in the elevation of mRNA and protein levels of LASS1 an… Show more

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Cited by 148 publications
(133 citation statements)
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“…It is very well-known that both exogenously applied C8-ceramide, PDMP, and SK-1 inhibitors elevate endogenous ceramide concentrations in various types of cancers [9,30]. In this study, we documented that inhibition of GCS and SK-1 with specific chemical inhibitors and exogenous C8:ceramide application inhibited cell proliferation and induced apoptosis in a dose-dependent manner in both K562 and Meg-01 CML cells.…”
Section: Discussionsupporting
confidence: 51%
See 1 more Smart Citation
“…It is very well-known that both exogenously applied C8-ceramide, PDMP, and SK-1 inhibitors elevate endogenous ceramide concentrations in various types of cancers [9,30]. In this study, we documented that inhibition of GCS and SK-1 with specific chemical inhibitors and exogenous C8:ceramide application inhibited cell proliferation and induced apoptosis in a dose-dependent manner in both K562 and Meg-01 CML cells.…”
Section: Discussionsupporting
confidence: 51%
“…We combined increasing concentrations of dasatinib with IC10 values of PDMP and SK-1 inhibitor since we have previously shown that IC10 values of these chemicals are enough to inhibit the enzyme activities and provide accumulation of ceramides in the cells [9]. In parallel experiments, we combined IC50 value of C8: ceramide with increasing concentrations of dasatinib since ceramide analogs trigger induction of generation of apoptotic ceramides at IC50 value [30]. The magic behind these experiments was to determine possible synergistic antiproliferative effects dasatinib on K562 and Meg-01 cells in which intracellular ceramide concentrations were increased.…”
Section: Measurement Of Cell Growth By Xttmentioning
confidence: 99%
“…found an association between ceramide C18:0 and depressive symptom severity in their study population (Demirkan et al., 2013). Importantly, both species have been implicated in apoptosis (Babenko, Hassouneh, Budvytiene, Liesiene, & Geilen, 2010; Cremesti et al., 2001; Grassme et al., 2001; Senkal et al., 2007; Thomas, Matsko, Lotze, & Amoscato, 1999). For ceramide C16:0, concentrations were found to be elevated in apoptotic cells within 2 hr of being exposed to ionizing radiation (Thomas et al., 1999).…”
Section: Discussionmentioning
confidence: 99%
“…C18:0 has been observed to induce apoptosis of keratinocytes in a concentration‐dependent manner (Babenko et al., 2010). In addition, concentrations of C18:0 were found to be elevated in chemotherapy‐induced apoptosis (Senkal et al., 2007). As both C16:0 and C18:0 may be proapoptotic, it is feasible that elevated concentrations of these species may contribute to neurodegeneration in depression.…”
Section: Discussionmentioning
confidence: 99%
“…Ceramide is an intracellular lipid that has been shown to regulate the activity of various biochemical and molecular targets involved in anti-proliferative responses and in cellular responses including oxidative stress and apoptosis [20,21]. The biological effects of ceramide depend on many parameters, such as cell type, nature of cell receptors, and their concentration [22].…”
Section: Introductionmentioning
confidence: 99%