Apoptosis induced by retinoic acid in Hep 3B cells in vitro

• Published in: Cancer letters Vol. 107; no. 1; pp. 149 - 159
• Main Authors: Kim, Dae Ghon, Jo, Baik Hwan, You, Kyung Ran, Ahn, Deuk Soo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.10.1996; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Carcinoma, Hepatocellular - pathology; Cell Cycle - drug effects; Cycloheximide - pharmacology; DNA, Neoplasm - analysis; General aspects; Hep 3B cells; Hepatom; Humans; Liver Neoplasms - pathology; Medical sciences; Microscopy, Electron; Pharmacology. Drug treatments; Protein Synthesis Inhibitors - pharmacology; Retinoic acid; Tretinoin - pharmacology; Hep 3B cells; Retinoic acid; Hepatom; Apoptosis; Antineoplastic agent; Human; Hepatic disease; Malignant tumor; Retinoids; In vitro; Liver cell carcinoma; Cell death; Established cell line; Digestive diseases; Tumor cell
• DOI: 10.1016/0304-3835(96)04407-2
• ISSN: 0304-3835

Human hepatoma Hep 3B cells underwent apoptosis in response to 100 μM all-trans retinoic acid (RA) in full serum (10% fetal calf serum) condition in vitro. Cell death began approximately 24 h following treatment, with more than 80% of the cells dead after 60 h. The dead cells, mainly detached cells, exhibited condensed chromatin and DNA fragmentation, which are indicative of endonuclease activation and are the hallmarks of apoptosis in epithelial cells. Concurrent exposure to 1 μM cycloheximide (CX) prevented approximately 50% of cell death and DNA fragmentation induced by RA. Thus, other toxic injury to the cells as well as apoptosis might be involved in cell death. Sixty hours exposure of RA decreased the percentage of cells in G 1 phase (16.3 ± 0.4% versus 52.4 ± 2.1%; P ≤ 0.01) and in G 2/M phase (13.4 ± 1.2% versus 21.2 ± 0.7%; P ≤ 0.01), but did not change percent of cells in S phase (20.8 ± 0.2% versus 20.7 ± 0.5%) of the cell cycle compared with control. RA may have caused accumulation of Hep 3B cells before G 1 phase, and that G 0 G 1 transition is a main check point in the active process of apoptosis. Electron micrographs of the cells treated with RA revealed typical morphologic changes of apoptosis, besides toxic injury to the cells. These data strongly indicate that RA is able to induce apoptosis and the induction of apoptosis may contribute to the antitumor activity of RA against hepatoma cells.