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c-Myc down-regulation increases susceptibility to cisplatin through reactive oxygen species-mediated apoptosis in M14 human melanoma cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Biroccio, Annamaria Benassi, Barbara Amodei, Sarah Gabellini, Chiara Bufalo, D. Del Zupi, Gabriella |
| Copyright Year | 2001 |
| Abstract | Our aim in this work was to define the role of c-Myc in the susceptibility to cisplatin [cis-diamminedichloroplatinum(II) (CDDP)] in human melanoma cells. Two M14 melanoma cell clones obtained by transfection and expressing six to ten times lower c-Myc protein levels than the parental cells and the control clone were employed. Analysis of survival curves demonstrates an increase in CDDP sensitivity in c-Myc low-expressing clones if compared with the control clone and the parental line. The enhanced sensitivity is unrelated to the impairment in enzymatic DNA repair activity. Cell cycle analysis demonstrates that although the control clone is able to completely recover from the CDDP-induced S-G(2)/M block, this arrest is prolonged in c-Myc low-expressing clones and a fraction of cells undergoes apoptosis. Although no changes in P53, Bax, Bcl-2, and Bcl-x(L/S) protein levels are observed, apoptosis is associated with the formation of reactive oxygen species (ROS), activation of caspase-1, caspase-3 and cleavage of the specific caspase substrate poly-ADP-ribose polymerase. The use of the antioxidant N-acetyl cysteine and caspase inhibitors prevents CDDP-induced apoptosis in c-Myc low-expressing clones, demonstrating that ROS, caspase-1, and caspase-3 are required for apoptotic cell death. Moreover, ROS generation depends on caspase-1-like activation because the Ac-YVAD-cho inhibitor abrogates CDDP-induced ROS in the c-Myc low-expressing clones. |
| Starting Page | 268 |
| Ending Page | 271 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/60/1/174.full.pdf |
| PubMed reference number | 11408612v1 |
| Volume Number | 60 |
| Issue Number | 1 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetylcysteine Adenosine Diphosphate Apoptosis Caspase Inhibitors Caspase-1 Cell Death Cisplatin Clone DNA Repair Down-Regulation MYC gene Poly A Reactive Oxygen Species Ribose caspase-3 |
| Content Type | Text |
| Resource Type | Article |
