Doxorubicin-induced F-actin reorganization in cofilin-1 (nonmuscle) down-regulated CHO AA8 cells.
The actin cytoskeleton plays an important role in many cellular processes, including cell mortality, mitosis, cytokinesis, intracellular transport, endocytosis and secretion but also is involved in gene transcription. The dynamics of the actin cytoskeleton is controlled by different classes of actin-binding proteins (ABPs) which regulate the polymerization of actin filaments. In this report we used siRNA against cofilin-1 (nonmuscle) to demonstrate the effect of cofilin on the nuclear and cytoplasmic actin pools in CHO AA8 cells after exposition to various concentrations of doxorubicin. The immunofluorescence studies showed doxorubicin dose dependent tendency to formation the multinucleated giant cells, but also the increase of fluorescence intensity of cofilin in nuclei of untransfected cells. Induction of cell death with doxorubicin treatment in untransfected cells revealed both mitotic catastrophe (in both lower and higher doxorubicin doses) and apoptosis (mostly in higher doxorubicin doses), whereas among cofilin-1 down-regulated cells we observed only mitotic catastrophe. The results suggest that cofilin has apoptosis-inducing ability and that mitotic catastrophe is independent from F-actin content in cell nucleus. In this point of view we conclude that different mechanisms of chromatin reorganization are involved in these two processes. Moreover, we suppose that apoptosis and mitotic catastrophe are independent from each other.
Department of Clinical Pathomorphology, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland. d_gr@wp.pl
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D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000502:physiology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D048749:Cytokinesis / Q000187:drug effects / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology
D000199:Actins; D000903:Antibiotics, Antineoplastic; D051338:Cofilin 1; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D004317:Doxorubicin