title: Synthetic retinoid CD437 promotes rapid apoptosis in malignant human epidermal keratinocytes and G1 arrest in their normal counterparts.
abstract: Four human cutaneous squamous cell carcinoma (SCC) cell lines and normal human epidermal keratinocyte (NHEK) cells from two donors were examined for sensitivity to the synthetic retinoid 6-[3-(1 -adamantyl)-4-hydroxyphenyl]-2-naph-thalene carboxylic acid (CD437) alone or in combination with other agents. CD437 promoted rapid (within 2 h) apoptosis in SCC cells and G1 arrest in NHEK cells. G1 arrest in NHEK cells was sustained for 48 h while apoptosis occurred in approximately 60% of SCC cell after 24 h. Apoptosis could not be inhibited by nuclear retinoic acid receptor antagonists or cycloheximide, indicating CD437 was functioning in a receptor-independent manner. All-trans retinoic acid not only failed to induce apoptosis in SCC cells even at 20-fold higher concentration relative to the effective concentration of CD437; it also decreased the efficacy of CD437. Because of its differential effects on normal versus malignant keratinocytes, CD437 may be useful for the prevention or treatment of cutaneous SCC.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030-4095, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hail
authors.forename: R
authors.initials: R
authors.lastname: Lotan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation; D004817:Epidermis / Q000473:pathology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D012176:Retinoids / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C099555:CD 437; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D012176:Retinoids; D014212:Tretinoin