Arsenic induces apoptosis through a c-Jun NH2-terminal kinase-dependent, p53-independent pathway
Huang, C; Ma, WY; Li, J; Dong, Z
HERO ID
627516
Reference Type
Journal Article
Year
1999
Language
English
PMID
| HERO ID | 627516 |
|---|---|
| In Press | No |
| Year | 1999 |
| Title | Arsenic induces apoptosis through a c-Jun NH2-terminal kinase-dependent, p53-independent pathway |
| Authors | Huang, C; Ma, WY; Li, J; Dong, Z |
| Journal | Cancer Research |
| Volume | 59 |
| Issue | 13 |
| Page Numbers | 3053-3058 |
| Abstract | Arsenic has been used as an effective chemotherapy agent for some human cancers, such as acute promyelocytic leukemia. In this study, we found that arsenic induces activation of c-Jun NH2-terminal kinases (JNKs) at a similar dose range for induction of apoptosis in JB6 cells. In addition, we found that arsenic did not induce p53-dependent transactivation. Similarly, there was no difference in apoptosis induction between cells with p53 +/+ or p53 -/-. In contrast, arsenic-induced apoptosis was almost totally blocked by expression of a dominant-negative mutant of JNK1. These results suggest that the activation of JNKs is involved in arsenic-induced apoptosis of JB6 cells. Taken together with previous findings that p53 mutations are involved in approximately 50% of all human cancers and nearly all chemotherapeutic agents kill cancer cells mainly by apoptotic induction, we suggest that arsenic may be a useful agent for the treatment of cancers with p53 mutation. |
| Pmid | 10397243 |
| Wosid | WOS:000081196400008 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | |WOS:000081196400008 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Animals; Apoptosis/*drug effects; Arsenic/*pharmacology; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism; Cell Adhesion; Cell Line; DNA Fragmentation; Epidermal Growth Factor/pharmacology; Genes, Reporter; Humans; JNK Mitogen-Activated Protein Kinases; Luciferases/genetics; Mice; *Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; *Transcription, Genetic; Transfection; Tumor Suppressor Protein p53/genetics/*metabolism; 0 (Tumor Suppressor Protein p53); 62229-50-9 (Epidermal Growth Factor); 7440-38-2 (Arsenic); EC 1.13.12.- (Luciferases); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); EC 2.7.11.24 (Mitogen-Activated Protein Kinases) |
| Is Qa | No |