Sphingolipid metabolism affects the anticancer effect of cisplatin

Li, Yulan; Lin, Ming-Lin; He, Songqing; Jin, Junfei

doi:10.5528/wjtm.v5.i1.37

Cited by 2 publications

(7 citation statements)

References 105 publications

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“…This would also be in agreement with the fact that long-chain Cer species seem to be relevant during AKI [40] and with previous observations of an increased SMase activity in the renal cortex during cisplatin treatment [33]. Cer is involved in cisplatin-induced apoptosis via signaling in both intrinsic and extrinsic pathways [39]. In the intrinsic mitochondrial pathway, cisplatin causes mitochondrial outer membrane permeabilization.…”

Section: Discussionsupporting

confidence: 90%

“…Sphingolipids are active lipids mainly found in the cell membranes and are quite rich in lipid rafts [37]. Ceramides are the central metabolites of sphingolipid metabolism, involving diverse molecules and enzymes with important roles in cellular processes, including cell growth, apoptosis, differentiation, drug resistance, and senescence [38,39]. Additionally, sphingolipids participate in the pathways related to cisplatin cancer cell death and AKI [33].…”

Section: Discussionmentioning

confidence: 99%

“…Cer can be transformed into more complex sphingolipids in the Golgi apparatus: phosphorylated to generate Cer-1-P, a signaling molecule; converted to SM by the action of SM synthase; or glycosylated to produce hesoxylceramides (glucosyl-or galactosyl-ceramides), precursors of sulfatides [38]. Cer can also be degraded to sphingosine, a precursor of sphingosine-1-phosphate (S1P), with important roles in cell survival and proliferation, inflammation, and drug resistance [39]. Finally, degradation of S1P to ethanolamine and hexadecenal is the exit pathway of this route [38].…”

Section: Discussionmentioning

confidence: 99%

“…In the intrinsic mitochondrial pathway, cisplatin causes mitochondrial outer membrane permeabilization. The increase in Cer, along with its downstream metabolites, can contribute to this permeabilization, and the channels' formation by Cer facilitates apoptosis in the mitochondrial membrane, allowing the entry of Bax into the mitochondrial outer membrane, as well as the outflow of cytochrome C [39]. Furthermore, Fas-mediated extrinsic apoptosis employs Fas receptor located in the lipid rafts, with its clustering being mediated by cisplatin-caused SMase activation and Cer elevation [39].…”

Section: Discussionmentioning

confidence: 99%

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Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Moreno-Gordaliza

Marazuela

Pastor

et al. 2021

IJMS

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Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Moreno-Gordaliza

Marazuela

Pastor

et al. 2021

IJMS

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“…Ceramide (Cer) is a second messenger in sphingolipid metabolism which can function as a potent tumor suppressor lipid to mediate cell death by triggering cell growth arrest as an inducer of apoptosis, necroptosis, and mitophagy [ 11 , 12 ]. Induction of ceramide generation has been characterized as another cytotoxic mode of cisplatin leading to ceramide-mediated mitochondrial apoptosis and/or ceramide-mediated death through the Fas pathway [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

Chueakwon

Jatooratthawichot

Talabnin

et al. 2022

Life

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Cholangiocarcinoma (CCA) is an aggressive tumor of the biliary epithelium with poor survival that shows limited response to conventional chemotherapy. Increased expression of glucosylceramide synthase (GCS) contributes to drug resistance and the progression of various cancers; the expression profiles of GCS (UGCG) and the genes for glucocerebrosidases 1, 2, and 3 (GBA1, GBA2, and GBA3) were therefore studied in CCA. The biological functions of GCS for cell proliferation and cisplatin sensitivity in CCA were explored. GCS expression was higher in CCA tumor tissues than that of GBA1, GBA2, and GBA3. Verification of GCS expression in 29 paired frozen CCA tissues showed that 8 of 29 cases (27.6%) had high GCS expression. The expression of GCS and GBA2 was induced in CCA cell lines following low-dose cisplatin treatment. Suppression of GCS by either palmitoylamino-3-morpholino-1-propanol (PPMP), GCS knockdown or a combination of the two resulted in reduced cell proliferation. These treatments enhanced the effect of cisplatin-induced CCA cell death, increased the expression of apoptotic proteins and reduced phosphorylation of ERK upon cisplatin treatment. Taken together, inhibition of the GCS increased cisplatin-induced CCA apoptosis via the inhibition of the ERK signaling pathway. Thus, targeting GCS might be a strategy for CCA treatment.

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Sphingolipid metabolism affects the anticancer effect of cisplatin

Cited by 2 publications

References 105 publications

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

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