APOPTOSIS INDUCTION AND CELL CYCLE PERTURBATION IN ESTABLISHED CELL LINES BY PEROXYSOMICINE A1 (T-514)

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) Vol. 24; no. 3; pp. 287 - 299
• Main Authors: Martinez, Francisco J., Zeng, Guo-Qing, Piñeyro, Alfredo, Garza-Ocañas, Lourdes, Tomei, L. David, Umansky, Samuil R.
• Format: Journal Article
• Language: English
• Published: New York, NY Taylor & Francis 01.08.2001; Informa Healthcare
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Anthracenes - toxicity; Antineoplastic agents; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; Caspase Inhibitors; Cell Cycle - drug effects; Cell Survival - drug effects; DNA Fragmentation - drug effects; DNA, Neoplasm - drug effects; Dose-Response Relationship, Drug; Flow Cytometry; General aspects; HeLa Cells - drug effects; HeLa Cells - pathology; Humans; Jurkat Cells - drug effects; Jurkat Cells - pathology; Medical sciences; Pharmacology. Drug treatments; Antineoplastic agent; Cell culture; Cell death; Cell cycle; Established cell line; Plant origin; Mechanism of action; In vitro; Biological activity; Apoptosis
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1081/DCT-100103725

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 G 2 /M phases of cell cycle indicating, most likely delay in G 2 . 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.