Estrogen receptor enhances the antiproliferative effects of trichostatin A and HC-toxin in human breast cancer cells.
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.
Min
Kyung Nan
KN
College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Cho
Min Jung
MJ
Kim
Dae-Kee
DK
Sheen
Yhun Yhong
YY
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000502:physiology*
D006131:Growth Inhibitors; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; D011960:Receptors, Estrogen; C012589:trichostatin A; C037654:HC toxin