title: Evidence supporting a role for mitochondrial respiration in apoptosis induction by the synthetic retinoid CD437.
abstract: Retinoids have been shown to modulate cell proliferation, differentiation, and apoptosis. It is thought that these effects mediate the chemopreventive and therapeutic effects of retinoids. Recently, some synthetic retinoids, including 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), have been found to induce apoptosis even in tumor cell lines that are resistant to all-trans retinoic acid. The proapoptotic activity of CD437 has been attributed to mitochondrial dysfunction via the induction of mitochondrial permeability transition (P. Marchetti et al., Cancer Res. 59: 6257-6266, 1999). The mechanistic aspects pertaining to how CD437 promotes changes in mitochondrial function are unclear. This study investigated the role of mitochondrial respiration in CD437-induced apoptosis. Human cutaneous squamous cell carcinoma COLO 16 cells were chronically exposed to ethidium bromide to inhibit mitochondrial DNA synthesis and produce respiration-deficient clones. These clones were exposed to CD437 (<or=10 microM) for 48 h and exhibited a marked resistance to mitochondrial permeability transition and apoptosis illustrating that mitochondrial respiration was required for these effects.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hail
authors.forename: E M
authors.initials: EM
authors.lastname: Youssef
authors.forename: R
authors.initials: R
authors.lastname: Lotan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects*; D012176:Retinoids / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C099555:CD 437; D012176:Retinoids