Roscovitine induces cell death and morphological changes indicative of apoptosis in MDA-MB-231 breast cancer cells

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 8; pp. 1903 - 1910
• Main Authors: MGBONYEBI, O. P, RUSSO, J, RUSSO, I. H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.04.1999
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - ultrastructure; Actins - metabolism; Antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Size - drug effects; Cell Survival - drug effects; Chemotherapy; Chromatin - metabolism; Cyclin-Dependent Kinases - antagonists & inhibitors; DNA, Neoplasm - biosynthesis; DNA, Neoplasm - drug effects; Humans; Medical sciences; Pharmacology. Drug treatments; Purines - pharmacology; Receptors, Estrogen - genetics; Tumor Cells, Cultured; Antineoplastic agent; Human; Mammary gland diseases; Carcinoma; Hormonoindependence; Established cell line; Cytotoxicity; Malignant tumor; Mammary gland; In vitro; Tumor cell; Apoptosis
• ISSN: 0008-5472; 1538-7445

We have previously shown (Mgbonyebi et al., Anticancer Res., 18: 751-756, 1998) that roscovitine, an olomoucine-related purine analogue and a selective inhibitor of cyclin-dependent kinases, inhibited the proliferative activity of human breast epithelial cells in vitro. The purpose of the present study was to identify the cellular processes and targets affected by roscovitine treatment in the estrogen receptor-negative MDA-MB-231 human breast carcinoma cells. Treatment of the cells with 10 microg/ml roscovitine daily for a length of time ranging from 24 to 240 h revealed that the compound inhibited DNA synthesis, induced cell death, and irreversibly inhibited the proliferative activity of the cells. Morphological analysis of roscovitine-treated cells by light and fluorescence microscopy demonstrated that this cyclin-dependent kinase inhibitor induced cell shrinkage, chromatin condensation, reorganization of actin microfilament architecture, and extensive detachment of cells from the cell culture substratum. These cellular events are all known to be associated with apoptosis. Collectively, the data generated from this study suggest that roscovitine induced apoptosis in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Because the efficacy of many anticancer drugs depends on their ability to induce apoptotic cell death, modulation of this parameter by roscovitine may provide a new chemopreventive and chemotherapeutic strategy for the clinical management of hormone-resistant breast cancers.