title: Actin disruption agents induce phosphorylation of histone H2AX in human breast adenocarcinoma MCF-7 cells.
abstract: Modified actin dynamics are a unique feature of transformed cancer cells and thereby promising targets for cancer chemotherapy. While latrunculin B (LB) and pectenotoxin-2 (PTX-2), both derived from natural sources, inhibit actin polymerization, jasplakinolide (JSP) prevents actin depolymerization. The purpose of this study was to examine the detailed molecular action of actin disruption inducing apoptosis via double strand breaks (DSBs). Actin disruption induced phosphorylation of H2AX, a well known DSB marker leading to G2 arrest and consequently resulted in apoptosis on MCF-7 cancer cells. Cells impaired by actin disruption activated Erk (extracellular signal-related kinase) and p53 protein was involved in DNA damage responses, but did not change the levels of p21Cip1/WAF1 protein in MCF-7 cells. To overcome the DSBs by actin disruption, MCF-7 cells set the repair system through the homologous recombination (HR) pathway. These results indicate that actin is involved in the signaling inducing DSBs and HR repair as well as G2 cell cycle arrest in human cancer. Therefore, the results suggest that actin disruption might be a potential candidate for developing anti-cancer therapies in human breast cancer.
authors.affiliation: Joint Research Center of Pusan National University-Fraunhofer IGB, Busan 609-735, Republic of Korea.
authors.forename: Ik Jae
authors.initials: IJ
authors.lastname: Shin
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Ahn
authors.forename: Yongkuk
authors.initials: Y
authors.lastname: Kim
authors.forename: Jong-Myoung
authors.initials: JM
authors.lastname: Kim
authors.forename: Won G
authors.initials: WG
authors.lastname: An
mesh_terms: D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011995:Recombination, Genetic; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C468783:H2AX protein, human; D006657:Histones; D053778:Thiazolidines; C037068:latrunculin B