Apoptosis induction and cell cycle perturbation in established cell lines by peroxysomicine A1 (T-514).

Abstract:

:Peroxysomicine A1, a novel potential anticancer compound induced cell death in established cell lines and in a primary culture of rat neonatal cardiomyocytes. Non-transformed cells are less sensitive to the compound than transformed cell lines. Fluorescent microscopy of dying cells stained with DNA-specific dyes revealed chromatin condensation and nuclear fragmentation as well as membrane blebbing characteristic of apoptosis. Flow cytometry of cells treated with peroxysomicine A1, demonstrated appearance of cells containing less than 2C DNA, that indicated degradation of nuclear DNA, another hallmark of apoptotic cell death. Z-VAD, a nonspecific caspase inhibitor, prevented DNA fragmentation but not cell death registered by permeabilization of cell outer membrane. Peroxysomicine A1 also inhibited proliferation of various cell lines. Flow cytometry analysis showed significant accumulation of dividing cells in G2/M phases of cell cycle indicating, most likely delay in G2. These results provide initial insight into the mechanisms of action of peroxysomicine A1 and suggest that peroxysomicine A1 is a potent inhibitor of cell proliferation and inducer of apoptosis and may be a useful antineoplastic chemotherapeutic agent.

journal_name

Drug Chem Toxicol

authors

Martinez FJ,Zeng GQ,Piñeyro A,Garza-Ocañas L,Tomei LD,Umansky SR

doi

10.1081/dct-100103725

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

287-99

issue

3

eissn

0148-0545

issn

1525-6014

journal_volume

24

pub_type

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