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