Background p53, a commonly mutated gene in human cancers, participates in cell cycle arrest, DNA repair and apoptosis. A small pharmacological compound, CP‐31398, was found to have the ability to promote proper p53 protein folding, activate p53 transcription of downstream targets, and slow tumour growth in mice. Additionally, CP‐31398 was found to be able to convert mutant p53 to wild‐type conformation in several cell lines.

Objectives To examine if CP‐31398 can revert all mutant p53 proteins to wild‐type function.

Methods We studied a series of apoptotic responses to CP‐31398 in three melanoma cell lines varying in p53 mutation status.

Results Upon a moderate dose of CP‐31398 treatment (15 µg mL⁻¹), only the wild‐type p53 MMRU and the single p53 point mutation MeWo cells exhibited apoptosis. Another melanoma cell line, Sk‐mel‐110, containing multiple p53 mutations, did not exhibit apoptosis. Although CP‐31398 enhanced overall p53 protein level, its ability to promote proper folding of p53 protein was limited to CP‐31398‐sensitive MMRU and MeWo cells. These sensitive cells showed an increased Bax and PUMA transcription, altered mitochondrial membrane potential, followed by the release of cytochrome c, and cleaved caspase‐9 and caspase‐3. We also demonstrated that Apaf‐1 was not involved in CP‐31398‐mediated apoptosis.

Conclusions Our results suggest that the ability of CP‐31398 to revert mutant p53 proteins to wild‐type conformation may be correlated to p53 mutational status. More studies are necessary, to further investigate the effect of CP‐31398 on mutant p53 and its potential applications as an anticancer agent.