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

López‐Marure, Rebeca; Gutiérrez, Gisela; Mendoza, Criselda; Ventura, Josep L.; Sánchez, Luis Sánchez; Maldonado, Elba Reyes; Zentella, Alejandro; Montaño, Luis F.

doi:10.1016/s0006-291x(02)00315-7

Cited by 33 publications

(21 citation statements)

References 34 publications

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“…Cer and 4,6-Diene-Cer Induce Apoptosis in MCF-7 Cells. Ceramide has been shown to reduce cell number by several mechanisms, including induction of cell death by both apoptotic and nonapoptotic mechanisms Lopez-Marure et al, 2002). We tested the hypothesis that treatment of MCF-7 cells with Cer induced apoptosis in our model system and that 4,6-diene-Cer initiated cell death in a similar manner.…”

Section: A Model Of Mcf-7 Chemoresistancementioning

confidence: 97%

“…The diversity of responses elicited by ceramide suggests the presence of distinct signaling pathways upon which ceramide acts. In the field of cancer biology, ceramide has been intensely studied for its ability to induce both apoptotic and nonapoptotic cell death Lopez-Marure et al, 2002). In tumor cells, chemotherapeutic drugs such as doxorubicin, vincristine, etoposide, and paclitaxel (Senchenkov et al, 2001), as well radiotherapy, increase intracellular ceramide levels after treatment (Haimovitz-Friedman, 1998).…”

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confidence: 99%

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Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer

Struckhoff¹,

Bittman²,

Burow³

et al. 2004

J Pharmacol Exp Ther

117

113

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Recent evidence suggests a role for aberrant ceramide levels in the pathogenesis of cancer and chemoresistance and indicates that manipulation of tumor ceramide levels may be a useful strategy in the fight against breast cancer. This study demonstrates that alterations in the degree and position of unsaturation of bonds in the sphingoid backbone of D-erythro-N-octanoyl-sphingosine (Cer) affect the antiproliferative ability of ceramide analogs in breast cancer cells. The most potent analog of Cer we tested is (2S,3R)-(4E,6E)-2-octanoylamidooctadecadiene-1,3-diol (4,6-diene-Cer), which contains an additional trans double bond at C(6)-C(7) of the sphingoid backbone. 4,6-Diene-Cer exhibited higher potency than Cer in tumor necrosis factor (TNF)-␣-resistant (IC 50 of 11.3 versus 32.9 M) and TNF-␣-sensitive (IC 50 of 13.7 versus 37.7 M) MCF-7 cells. 4,6-Diene-Cer was also more potent than Cer in inducing cell death in MDA-MB-231 and NCI/ADR-RES breast cancer cell lines (IC 50 of 3.7 versus 11.3 M, and 24.1 versus 86.9 M, respectively). 4,6-Diene-Cer caused a prolonged elevation of intracellular ceramide levels in MCF-7 cells, which may contribute to its enhanced cytotoxicity. Furthermore, treatment of MCF-7 cells with Cer or 4,6-diene-Cer resulted in induction of apoptosis by 8 h via the mitochondrial pathway, as demonstrated by release of cytochrome c, loss of membrane asymmetry (measured by Annexin V staining), and a decrease in the mitochondrial membrane potential. Importantly, both Cer and 4,6-diene-Cer displayed selectivity toward transformed breast cells over nontransformed breast epithelial cells. These data suggest that these and other novel ceramide analogs represent potential therapeutic agents in breast cancer treatment.

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Section: A Model Of Mcf-7 Chemoresistancementioning

confidence: 97%

mentioning

confidence: 99%

Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer

Struckhoff¹,

Bittman²,

Burow³

et al. 2004

J Pharmacol Exp Ther

117

113

View full text Add to dashboard Cite

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“…13) A cerebroside from vegetable oil has been recognized in vitro for its capacity to inhibit aggregation of washed rabbit platelet. 14) From a modern viewpoint, sea cucumber is a valuable source of certain bioactive substances, including collagen, 15) polysaccharides, 16) triterpenoid saponins, 17) cerebrosides, 5) and gangliosides, 18) which can serve as natural health products and can be developed into drugs. Acaudina molpadioides is a low-value sea cucumber widely distributes around sandy coastal regions of China with abundant production.…”

mentioning

confidence: 99%

Isolation and Anti-Fatty Liver Activity of a Novel Cerebroside from the Sea CucumberAcaudina molpadioides

Wang

Feng

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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“…In agreement with previous studies also showing protection by Bcl-2 overexpression, 24,25 our observations suggest that the ceramide analogs activate the apoptotic machinery upstream of the mitochondria. In addition, as reported for short-chain ceramides, 11,[31][32][33][34] the ceramide analogs trigger a non-apoptotic form of cell death because caspase inhibitors did not completely block membrane permeability alterations, phosphatidylserine externalization, morphological changes and cell death.…”

Section: Ceramide Analogs Trigger Jurkat Cell Death T Granot Et Almentioning

confidence: 64%

“…Addition of synthetic short-chain ceramides, ceramines, C16-or C18-serinols, cationic ceramides as well as some other analogs was reported to mimic ceramide in inducing apoptosis in various cancer or leukemia cell lines, and, in some instances, to reduce the mass of xenografted tumors. [6][7][8][9][10][11][12][13][14][15] These observations have emphasized the potential usefulness of developing novel, ceramide-based chemotherapeutic agents for anticancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Caspase-dependent and -independent cell death of Jurkat human leukemia cells induced by novel synthetic ceramide analogs

et al. 2006

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Ceramide metabolism has emerged as a potential target for anticancer therapy. Here, the potential usefulness of two novel synthetic ceramide analogs as anti-leukemic drugs was investigated. Compounds AD2646 and AD2687 were able to dose-and time-dependently decrease the viability of Jurkat leukemic cells. This was accompanied by an accumulation of endogenous ceramide owing to perturbed ceramide metabolism. Cytotoxicity involved caspase activation but also necrotic-like features, as evidenced by phosphatidylserine externalization, membrane permeability, hypodiploidy, caspase processing and only partial protection from cell death by a pan-caspase inhibitor. Ceramide analogs also induced cell death in Jurkat mutants that are deficient in cell death signaling proteins, including FADD, caspase-8 and 10, and RIP. While overexpression of Bcl-xL did not suppress ceramide accumulation, it conferred robust protection from caspase activation and cell death. Altogether, these novel ceramide analogs are able to kill leukemic cells through distinct pathways implicating caspase activation and mitochondrial events, and represent a new group of bioactive molecules with potential applications in anticancer therapy.

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

Cited by 33 publications

References 34 publications

Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer

Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer

Isolation and Anti-Fatty Liver Activity of a Novel Cerebroside from the Sea CucumberAcaudina molpadioides

Caspase-dependent and -independent cell death of Jurkat human leukemia cells induced by novel synthetic ceramide analogs

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