A novel cisplatin mediated apoptosis pathway is associated with acid sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer

We report here that these DNA-damaging agents, particularly cisplatin, induce apoptosis through plasma membrane disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways. Our objectives were to: quantify the composition of membrane metabolites; and determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS-mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting analysis revealed enhanced apoptosis as measured by: increased phosphocholine, and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and nucleoside triphosphate concentrations. The plasma membrane alterations were accompanied by increased ASMase activity, leading to the upregulation of FAS, FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA, CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase activity and the intrinsic pathways in cisplatin-mediated membrane demise, and contribute to our understanding of the mechanisms by which ovarian tumors may become resistant to cisplatin.
Source: Apoptosis - Category: Molecular Biology Source Type: research

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Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
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Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Female Pelvic Medicine and Reconstructive Surgery - Category: OBGYN Tags: Review Article Source Type: research
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Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
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Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
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Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
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Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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