title: Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines.
abstract: Deregulation of crucial embryonic pathways, including hedgehog signaling, has been frequently implicated in a variety of human cancers and is emerging as an important target for anticancer therapy. This study evaluated the potential anticancer effects of cyclopamine, a chemical inhibitor of hedgehog signaling, in human malignant mesothelioma (HMM) cell lines. Cyclopamine treatment significantly decreased the proliferation of HMM cells by promoting apoptosis and shifting the cell cycle toward dormant phase. The clonogenicity and mobility of HMM cells were significantly decreased by cyclopamine treatment. Treatment of HMM cells with cyclopamine significantly reduced the abundance of side population cells, which were measured using an assay composed of Hoechst 33342 dye staining and subsequent flow cytometry. Furthermore, the expression levels of stemness-related genes were significantly affected by cyclopamine treatment. Taken together, the present study showed that targeting hedgehog signaling could reduce a more aggressive subpopulation of the cancer cells, suggesting an alternative approach for HMM therapy.
authors.affiliation: 1] Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea [2] BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: H-A
authors.initials: HA
authors.lastname: Kim
authors.affiliation: 1] Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea [2] BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: M-C
authors.initials: MC
authors.lastname: Kim
authors.affiliation: 1] Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea [2] BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: N-Y
authors.initials: NY
authors.lastname: Kim
authors.affiliation: 1] Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea [2] Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D058990:Molecular Targeted Therapy / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D014053:Tomatine / Q000031:analogs & derivatives / Q000494:pharmacology; D014704:Veratrum Alkaloids / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053823:Hedgehog Proteins; D014704:Veratrum Alkaloids; C003677:tomatidine; D014053:Tomatine; C000541:cyclopamine