title: Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.
abstract: 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.
authors.forename: Mengli
authors.initials: M
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, 12 jiang-wang-miao street, Nanjing 210042, China. mpc815@163.com.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Ma
authors.forename: Dechuan
authors.initials: D
authors.lastname: Wang
authors.forename: Chundi
authors.initials: C
authors.lastname: He
authors.forename: Yuping
authors.initials: Y
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015474:Isotretinoin / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C000608162:N-(4-ethoxycarbonylphenyl)isoretinamide; D018168:Receptors, Retinoic Acid; D018808:Transcription Factor AP-1; D015474:Isotretinoin