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ERK activation increases nitroprusside induced apoptosis in human melanoma cells irrespective of p53 status: Role of superoxide dismutases
| Content Provider | Scilit |
|---|---|
| Author | Gomez–Sarosi, Luis Alberto Strasberg–Rieber, Mary Rieber, Manuel |
| Copyright Year | 2009 |
| Description | Journal: Cancer Biology & Therapy Constitutive ERK activation, superoxide dismutases (SOD) and p53 mutations are implicated in modulating tumor apoptotic response. We now investigated whether human melanoma survival in response to sodium nitroprusside (SNP) is modulated by: a) stable introduction of a DN- mutant p53 ; b) pharmacologically inhibiting ERK activation with UO126 ; c) addition of exogenous SOD. Nitroprusside releases nitric oxide (NO) when intact , or acts in a NO-independent manner via iron and residual cyanide after light exposure (lex-SNP) . When tested at 300 µM in 72 hour treatments by cytometric live-dead assays , intact SNP caused a 50 % lethality versus a 30 % lethality induced by lex-SNP. No protection from SNP toxicity was seen when inhibiting the PI3-kinase pathway with LY294002 or c-Jun NH(2) kinase signaling with SP600125. However , pretreatment with UO126 protected from SNP –mediated cell death including counteracting apoptosis-associated Bax expression and PARP cleavage, plus reversing loss of Cu,Zn-SOD. Moreover , addition of exogenous SOD also protected cells from SNP toxicity. In spite of the greater earlier effects of intact SNP, cells treated with single doses of either intact or lex-SNP, revealed about a 90 % mortality in longer 120 hour treatments, and these were also counteracted by UO126 or exogenous SOD. This report is the first to show that: constitutive ERK activation characteristic of cancer cells, increases a nitroprusside-induced apoptosis modulated by SOD. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.8.12.8561?needAccess=true |
| Ending Page | 1182 |
| Page Count | 10 |
| Starting Page | 1173 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.8.12.8561 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 12 |
| Volume Number | 8 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2009-06-15 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Biochemistry and Molecular Biology Hour Treatments Constitutive Nitroprusside Induced Apoptosis Increases a Nitroprusside Addition of Exogenous |
| Content Type | Text |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
