Induced differentiation in HT29, a human colon adenocarcinoma cell line.
The human colon adenocarcinoma cell line HT29 displays an undifferentiated phenotype under standard growth conditions. When these cells were cultured for 21 days and then treated with forskolin, most of the cells formed brush borders on their apical surfaces. Brush border formation was inhibited by cytochalasin D but not by colchicine. Colchicine, nocodazole and taxol were found to induce differentiation and apoptosis in HT29 cells. Differentiation was characterized by flattening of the cells, formation of brush borders on apical surfaces and tight junctions between adjacent cells. Apoptosis was characterized by detachment of round cells from the cell layer, condensation of nuclear DNA and annexin V binding to cell surfaces. Treatment with colchicine or forskolin induced the association of E-cadherin to the cytoskeleton fraction of subconfluent HT29 cells. This effect was less prominent in post confluent cells. Our data indicate that microtubule-interfering agents may serve as an important tool in the study of differentiation and apoptosis in intestinal carcinoma.
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
E
E
Cohen
I
I
Ophir
Y B
YB
Shaul
D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000032:analysis / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D003078:Colchicine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D005614:Freeze Fracturing; D019073:HT29 Cells / Q000737:chemistry / Q000166:cytology* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D008871:Microvilli / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D019108:Tight Junctions / Q000502:physiology
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D019384:Nucleic Acid Synthesis Inhibitors; D005576:Colforsin; D015638:Cytochalasin D; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine