RT Journal Article SR Electronic T1 Gross Thymic Extract, Thymax, Induces Apoptosis in Human Breast Cancer Cells In Vitro through the Mitochondrial Pathway JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1603 OP 1609 VO 28 IS 3A A1 GHONEUM, MAMDOOH A1 SETO, YOSHIKAZU A1 SATO, SHIZUO A1 GHONEUM, ALIA A1 BRAGA, MELISSA A1 GOLLAPUDI, SASTRY YR 2008 UL http://ar.iiarjournals.org/content/28/3A/1603.abstract AB Previous studies have shown that thymic extracts possess antitumor and antimetastatic properties, but the mechanisms are not completely understood. Therefore, in this study the ability of the gross thymic extract Thymax to induce apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated. Tumor cells were cultured with different concentrations of Thymax for 24 h and the apoptotic response was assessed by propidium iodide and TUNEL assays. Activation of caspases and changes in mitochondrial membrane potential (MMP) were monitored by flow cytometry and the expression of Bcl-2 and Bax was determined by Western blot analysis. Thymax induced apoptosis in monolayer MCF-7 cells in a dose-dependent manner; at concentrations of 2.5, 5 and 10% (v/v) it caused 9%, 10% and 25% apoptosis, respectively, as compared to 6% for control cancer cells without treatment. The induction of apoptosis by Thymax was associated with activation of caspases 8 and 9, and the addition of a pan caspase inhibitor partially inhibited Thymax-induced apoptosis by 20% . In addition, the MMP was decreased significantly at Thymax concentrations of 5%-20%, which was associated with a decrease in the protein expression of Bcl-2 and an increase in Bax. These results suggest that Thymax exerts its effects via the mitochondrial pathway of apoptosis and may represent a new class of adjuvants for the treatment of breast cancer. Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved