Effects of a novel antitumor depsipeptide, FR901228, on human breast cancer cells.
Human breast cancer MCF7 and MDA-MB231 cells were used to investigate the biological and molecular activities of a novel naturally occurring agent, FR901228 (FR), that possesses a potent antitumor activity against human and murine tumor cells. Investigation of the cytotoxicity of FR and induction of internucleosomal DNA degradation in FR-treated cultures revealed that FR induced apoptotic-like cell death of MCF7 and MDA-MB231 cells. In FR-treated apoptotic cultures, flow cytometry revealed that there was a significant decrease of cells in S phase of the cell cycle. In FR-treated cells there was an increased expression of p21Cip1 and phosphorylation of Bcl-2 as determined by Western immunoblotting, and a novel cytoplasmic kinase of 33 kDa, p33 kinase, as determined by the in-gel kinase assay using myelin basic protein (MBP) as a substrate. Increased expression of p21CiP1, phosphorylation of Bcl-2, and activation of p33 MBP kinase may play part of the key mechanism for FR-induced apoptosis.
Rajgolikar
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G
Developmental Therapeutics Program, The Ohio State University Comprehensive Cancer Center, Columbus, USA.
Chan
K K
KK
Wang
H C
HC
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D047630:Depsipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010456:Peptides, Cyclic; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D047630:Depsipeptides; D010456:Peptides, Cyclic; D019253:Proto-Oncogene Proteins c-bcl-2; C087123:romidepsin; D011494:Protein Kinases