The p53-stabilizing compound, CP-31398, does not enhance chemosensitivity in human melanoma cells.
BACKGROUND
Malignant melanoma is a life-threatening disease with a poor prognosis due to its capacity for rapid metastasis and resistance to radio- and chemo-therapy. A pharmacological compound, CP-31398, was recently found to be able to stabilize wild-type p53 and rescue mutant p53 to enhance its transcriptional activity and suppress tumor growth in mice. Since many chemotherapeutic drugs induce p53-dependent apoptosis, we sought to investigate if CP-31398 would enhance chemosensitivity in human melanoma cells by stabilizing p53.


METHODS
Human melanoma cell lines carrying either wild-type or mutant p53 were treated with CP-31398 and anticancer drugs, and the rate of cell survival or apoptosis was determined by sulforhodamine B, propidium iodide staining and flow cytometry. The p53 protein levels were determined by Western blotting.


RESULTS
A non-toxic dose of CP-31398 elevated p53 protein levels in a wild-type (MMRU) and a mutant (Sk-mel-110) p53 melanoma cell line, but did not enhance cell death induced by camptothecin. Furthermore, pretreatment with CP-31398 did not enhance camptothecin-induced apoptosis or elevate p53 protein induction. In addition, pretreatment of MMRU with CP-31398 did not enhance cell death induced by cisplatin or vincristine.


CONCLUSIONS
CP-31398 does not enhance chemosensitivity in human melanoma cells.
Luu
Yvonne
Y
Department of Medicine, Division of Dermatology, Vancouver Hospital, Health Sciences Centre, University of British Columbia, Vancouver, BC, Canada.
Li
Gang
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology
D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; C402665:CP 31398; D002945:Cisplatin; D002166:Camptothecin