Decreased thymosin β4 in apoptosis induced by a variety of antitumor drugs

As many antitumor drugs can kill tumors through the induction of apoptosis, the effect of these drugs presumably would be enhanced ii they were used in combination with other drugs that interact with apoptotic processes. To clarify the biological events involved in the induction of apoptosis, we examined changes in the proteins associated with induction of apoptosis by antitumor drugs. When Molt-4 cells were exposed to the antitumor drugs etoposide, meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane (ICRF-193), and neocarzinostatin, they exhibited apoptotic cell death as determined by flow cytometry using fluorescein isothiocyanate (FITC)-labeled annexin V staining of phosphatidylserine on membranes and detection of hypodiploid cells. Following the induction of apoptosis, a low molecular weight protein that was identified to be thymosin beta(4) by HPLC analysis was commonly decreased, and the morphology of actin filaments changed into clump formations. These results suggest that decreased thymosin beta(4) is involved in the induction of apoptosis hy antitumor drugs. (C) 1999 Elsevier Science Inc.