Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers
worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive
and therapeutic agents for a variety of human cancers including CSCC. In this study we
synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and
possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous
carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal
keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2,
CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition
of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid
receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that
ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC.
Keywords: AP-1, cell cycle arrest, cutaneous squamous cell carcinoma, ECPIRM, MAPK, N-(4-ethoxycarbonylphenyl) isoretinamide.
Rights & PermissionsPrintExport