Acceleration of dna damage-induced apoptosis in leukemia cells by interfering with actin system

• Published in: Experimental hematology Vol. 28; no. 12; p. 1491
• Main Authors: Yamazaki, Y., Dang, Y., Shang, X., Tsuruga, M., Fujita, Y., Tanaka, H., Zhou, D., Kawasaki, K., Oka, S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-12-2000
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(00)00628-7

The apoptosis induced by actinomycin D (AD) in human mega-karyoblastic leukemia CMK-7 cell line is accelerated by microtubule poisons such as colcemid. We previously reported that the cell fragmentation in this apoptosis was suppressed by cytochalasin D (CD).
1 Here, we report that the AD-induced apoptosis is also accelerated by CD. The caspase-3 activation and DNA cleavage reached the maximum at least 10 hr earlier in the presence of CD than without this actin polymerization inhibitor. Decrease in organelle membrane potential, cytochrome
c release from mitochondria, and cleavage of procaspase-9 to its active form began to appear prior to the caspase-3 activation. Apaf-1 was detected in the cytosol. These results suggest that the autocatalytic activation of caspase-9 starts the usual caspase cascade, and that the determinant, cytochrome
c liberation, is promoted by interfering with the actin system. The cell surface F-actin disappeared by the AD-CD treatment and instead broad actin fibers appeared in the nucleus. These fibers were remote from the condensed chromatins, while F-actin in the cells undergoing apoptosis without CD accumulated around the nuclear fragments. The acceleration of AD-induced apoptosis by CD was found in U937 cells as well. Apoptosis induced by other DNA damaging agents (CDDP and MMC) was also accelerated by CD. The apoptosis by AD and CD was counteracted by antioxidants such as α-tocopherol and luteolin. Thus, the DNA damage-induced apoptosis is affected by disruption of the actin system, and probably, reactive oxygen species are involved in the process.
1
Exp. Hematol., 27, Suppl. 1, 51 (1999).