eprintid: 20539 rev_number: 29 userid: 1419 dir: disk0/00/02/05/39 datestamp: 2014-02-14 17:03:26 lastmod: 2021-06-12 22:55:45 status_changed: 2014-02-14 17:03:26 type: article metadata_visibility: show item_issues_count: 0 eprint_status: archive creators_name: Lazo, JS creators_name: Tamura, K creators_name: Vogt, A creators_name: Jung, JK creators_name: Rodriguez, S creators_name: Balachandran, R creators_name: Day, BW creators_name: Wipf, P creators_email: lazo@pitt.edu creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: pwipf@pitt.edu creators_id: LAZO creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: PWIPF title: Antimitotic actions of a novel analog of the fungal metabolite palmarumycin CP1 ispublished: pub divisions: sch_as_chemistry full_text_status: public abstract: The pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities but their antineoplastic effects are not well established. We have examined their antiproliferative actions against tumor cells using a temperature-sensitive tsFT210 mouse mammary carcinoma cell line and found that a novel palmarumycin analog, [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4- spiro-2′-naphtho [1″,8″-de][1′,3′][dioxin] or SR-7, prominently blocked mammalian cell cycle transition in G2/M but not in G1 phase. We found no evidence for inhibition of the critical mitosis-controlling cyclin-dependent kinase Cdk1, or its regulator, the dual specificity phosphatase Cdc25. Moreover, Cdk1 was hypophosphorylated and not directly inhibited by SR-7. SR-7 also failed in vitro to hypernucleate bovine tubulin, did not compete with colchicine for tubulin binding, and only modestly blocked GTP-induced assembly. In addition, SR-7 caused almost equal inhibition of paclitaxel-sensitive and -resistant cell growth. Moreover, unlike benchmark tubulin-disrupting agents, SR-7 did not cause hyperphosphorylation of the antiapoptotic protein Bcl-2. Thus, SR-7 represents a novel chemical structure that can inhibit G2/M transition by a mechanism that appears to be independent of marked tubulin disruption. date: 2001-02-14 date_type: published publication: Journal of Pharmacology and Experimental Therapeutics volume: 296 number: 2 pagerange: 364 - 371 refereed: TRUE issn: 0022-3565 pmid: 11160619 mesh_headings: Animals mesh_headings: Antineoplastic Agents--pharmacology mesh_headings: Binding, Competitive--drug effects mesh_headings: Blotting, Western mesh_headings: Breast Neoplasms--metabolism mesh_headings: Breast Neoplasms--pathology mesh_headings: Cell Division--drug effects mesh_headings: Colchicine--metabolism mesh_headings: Cyclin-Dependent Kinases--metabolism mesh_headings: Dioxanes--pharmacology mesh_headings: Female mesh_headings: Fibroblasts--drug effects mesh_headings: Flow Cytometry mesh_headings: Humans mesh_headings: Mice mesh_headings: Naphthalenes mesh_headings: Phosphoric Monoester Hydrolases--metabolism mesh_headings: Phosphorylation mesh_headings: Proto-Oncogene Proteins c-bcl-2--metabolism mesh_headings: Receptors, Estrogen--drug effects mesh_headings: Spiro Compounds--pharmacology mesh_headings: Tubulin--metabolism mesh_headings: Tumor Cells, Cultured mesh_headings: Tumor Suppressor Protein p53--metabolism chemical_names: Antineoplastic Agents chemical_names: Dioxanes chemical_names: Naphthalenes chemical_names: Proto-Oncogene Proteins c-bcl-2 chemical_names: Receptors, Estrogen chemical_names: Spiro Compounds chemical_names: Tubulin chemical_names: Tumor Suppressor Protein p53 chemical_names: palmarumycin CP(1) chemical_names: Cyclin-Dependent Kinases chemical_names: Phosphoric Monoester Hydrolases chemical_names: Colchicine citation: Lazo, JS and Tamura, K and Vogt, A and Jung, JK and Rodriguez, S and Balachandran, R and Day, BW and Wipf, P (2001) Antimitotic actions of a novel analog of the fungal metabolite palmarumycin CP1. Journal of Pharmacology and Experimental Therapeutics, 296 (2). 364 - 371. ISSN 0022-3565 document_url: http://d-scholarship-dev.library.pitt.edu/20539/1/licence.txt