title: Inhibition of macromolecular synthesis by cryptophycin-52.
abstract: Cryptophycin (CP)-52, a synthetic analog of CP-1, possesses potent and selective antiproliferative activity against human solid tumors both and. Based on an algorithm developed in this laboratory using HCT-116 human colon adenocarcinoma cells, CP-52 exhibited a time- and concentration-dependent antiproliferative effect in the clonogenic assay. Inhibition of both DNA and RNA synthesis was observed in the absence of any effect on protein synthesis following a 24-h exposure to CP-52, at a time when proliferating cells were arrested in the G2/M phase of the cell cycle. In summary, we interpret these data to indicate that the selective inhibition of DNA synthesis may be a major causative factor responsible for the antiproliferative activity of CP-52 and subsequent G2/M arrest.
authors.affiliation: Drug Discovery and Development Program, Josephine Ford Cancer Center, Henry Ford Health System, Detroit, MI 48202-3450, USA. bsubram1@hfhs.org
authors.forename: Balanehru
authors.initials: B
authors.lastname: Subramanian
authors.forename: Alexander
authors.initials: A
authors.lastname: Nakeff
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Media
authors.forename: Richard A
authors.initials: RA
authors.lastname: Wiegand
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Valeriote
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis*; D047630:Depsipeptides; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007769:Lactams / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D008677:Metaphase / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D004247:DNA; C114033:cryptophycin 52