Estrogen receptor enhances the antiproliferative effects of trichostatin A and HC-toxin in human breast cancer cells.

Abstract

Trichostatin A, an antifungal antibiotics, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest. In this study, the antiproliferative activities of trichostatin A and HC-toxin were compared between estrogen receptor positive human breast cancer cell MCF-7 and estrogen receptor negative human breast cancer cell MDA-MB-468. Trichostatin A and HC-toxin showed potent antiproliferative activity in both MCF-7 and MDA-MB-468 cells. In MCF-7 cells that contain high level estrogen receptor, trichostatin A and HC-toxin brought about three-times more potent cell growth inhibitory effect than estrogen receptor negative MDA-MB-468 cells. Both trichostatin A and HC-toxin showed cell cycle arrest at G2/M phases of MCF-7 and MDA-MB-468 cells in a dose- and time-dependent manner. Trichostatin A and HC-toxin also induced apoptosis from MCF-7 and MDA-MB-468 cells in a dose- and time-dependent manner. Results of this study suggested that antiproliferative effects of trichostatin A and HC-toxin might be involved in estrogen receptor signaling pathway, but cell cycle arrest and apoptosis of trichostatin A and HC-toxin might not be involved in estrogen receptor system of human breast cancer cells.

• Authors: Kyung Nan Min, Min Jung Cho, Dae-Kee Kim, Yhun Yhong Sheen
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 27 Issue 5 Pg. 554-61 (May 2004) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 15202563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Growth Inhibitors
• Hydroxamic Acids
• Peptides, Cyclic
• Receptors, Estrogen
• trichostatin A
• HC toxin

Topics

• Apoptosis (drug effects, physiology)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Synergism
• Growth Inhibitors (pharmacology, therapeutic use)
• Humans
• Hydroxamic Acids (pharmacology, therapeutic use)
• Peptides, Cyclic (pharmacology, therapeutic use)
• Receptors, Estrogen (physiology)