Genistein induces apoptosis in T lymphoma cells via mitochondrial damage.
The soy isoflavone genistein has been identified as having antiproliferative and apoptotic effects on various malignant cell types derived from solid tumors. Because little information regarding the effect of genistein on hematopoietic malignancies is available, we undertook this study of T-cell lymphomas. We tested the effect of genistein on murine T-cell lines derived from thymic lymphomas induced by an oncogenic murine leukemia virus. When T lymphoma cells were treated with genistein concentrations of 15 microM and greater, it was observed that the percentage of viable cells was significantly reduced in a dose- and time-dependent manner. The observed cell killing was found to be the result of apoptosis as detected by flow cytometric analysis of cells stained with annexin V and propidium iodide and assays for caspase-3 activation and DNA fragmentation. Cell staining with the mitochondrial specific dye JC-1 and detection of caspase-9 activation revealed that genistein produced mitochondrial depolarization as an early step in the induction of apoptosis. Bongkrekic acid inhibition of mitochondrial depolarization identified the mitochondria permeability transition pore (PTP) as a potential target of genistein activity. These results indicate that the induction of apoptosis by pharmacological concentrations of genistein in T lymphoma cells occurs via mitochondrial damage with the involvement of the PTP.
Baxa
Dwayne M
DM
Infectious Disease Research, Henry Ford Health System, Detroit, MI 48202, USA.
Luo
Xixia
X
Yoshimura
Fayth K
FK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D013997:Time Factors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019833:Genistein; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases