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| Initiation of growth arrest and apoptosis of MCF-7 mammary carcinoma cells by tributyrin, a triglyceride analogue of the short-chain fatty acid butyrate, is associated with mitochondrial activity |
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| Author(s): Heerdt BG, Houston MA, Anthony GM, Augenlicht LH |
| Source: CANCER RESEARCH Volume: 59 Issue: 7 Pages: 1584-1591 Published: APR 1 1999 |
| Times Cited: 51 References: 66 |
| Abstract: we investigated the effects of tributyrin, a triglyceride analogue of the short-chain fatty acid butyrate and an approved food additive, establishing induction of growth arrest and apoptosis of MCF-7 human mammary carcinoma cells. Transient increased mitochondria-associated bar, dissipation of the mitochondrial membrane potential (Delta Psi(m)), and caspase-3-independent cleavage of poly(ADP-ribose) polymerase are evident as early as 4 h after treatment of cells with tributyrin. These events are followed by the transient accumulation of mitochondrial cytochrome c in the cytosol and, finally, the generation and accumulation of cells with subdiploid DNA content. During the period in which mitochondria-associated bar levels are elevated, the Delta Psi(m) is disrupted, and cytochrome c is detected in the cytosol, we show induction of p21(WAF1/Cip1) the absence of increased p53 and arrest of cells in G(2)-M. Thus, early mitochondria-associated events may play a key role in initiating and/or coordinating tributyrin-mediated growth arrest and apoptosis of wild-type p53 MCF-7 cells. Because effective chemoprevention has been associated with agents that restore or maintain the balance between proliferation and apoptosis, dietary tributyrin, particularly during the critical period of mammary gland development, may be a promising chemopreventive agent. |
| Document Type: Article |
| Language: English |
| Reprint Address: Heerdt, BG (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol Hofheimer 511, 111 E 210th St, Bronx, NY 10467 USA |
Addresses:
1. Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol Hofheimer 511, Bronx, NY 10467 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 182ZJ |
| ISSN: 0008-5472 |
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