title: Antitumor effect of suberoylanilide hydroxamic acid and topotecan in renal cancer cells.
abstract: The treatment modality for advanced renal cancer is limited. The development of novel systemic therapies has long been waited for. Suberoylanilide hydroxamic acid (SAHA) is one of the most potent histone deacetylase (HDAC) inhibitors, which are promising novel anticancer agents. SAHA has already been tested in phase II clinical trials; however, its effectiveness has been found to be limited. Recently, the combination of SAHA and topoisomerase I inhibitor, topotecan, was shown to be effective, but this treatment strategy has not been tested in renal cancer cells. In the present study, we found that the combination of SAHA and topotecan effectively inhibited the growth of renal cancer cells by suppressing the expression of cyclin-dependent kinase (CDK) 4 and cyclin D1, and promoting retinoblastoma protein (Rb) dephosphorylation. Furthermore, the combination therapy was found to inhibit both the function and expression of HDACs, which may be one of the main mechanisms of the combination therapy. To the best of our knowledge, this is the first report that has revealed the combined beneficial effect of SAHA and topotecan on renal cancer cells. Combining SAHA and topotecan is thus a promising approach to the treatment of renal cancer.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan. zenpaku@ndmc.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Akio
authors.initials: A
authors.lastname: Horiguchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Sumitomo
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
mesh_terms: D000107:Acetylation; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000032:analysis; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019772:Topotecan / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D019938:Cyclin D1; D000077337:Vorinostat; D019772:Topotecan; D051358:Cyclin-Dependent Kinase 4; D006655:Histone Deacetylases