Induction of Senescence in Diterpene Ester-Treated Melanoma Cells via PKC-dependent Hyperactivation of the MAPK Pathway

ABSTRACT: The diterpene ester PEP005 is a novel anticancer agent that activates PKC and cures subcutaneous murine melanoma by topical application. We now describe the in vitro cytostatic effects of PEP005 and the diterpene ester TPA, observed in 20% of human melanoma cell lines. Primary cultures of normal human neonatal fibroblasts were uniformly resistant to growth arrest, indicating a potential for tumor selectivity. Sensitive cells were induced to senesce and exhibited a G1 and G2/M arrest. There was sustained expression of p21WAF1/CIP1, irreversible dephosphorylation of the retinoblastoma gene product (Rb) and transcriptional silencing of E2F-responsive genes in sensitive cell lines. Activation of MEK1/2 by PKC was required for diterpene ester-induced senescence. Expression profiling revea

ORGANISM(S): Homo sapiens

SUBMITTER: Steven Ogbourne 

PROVIDER: E-GEOD-3484 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress