title: Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells.
abstract: Double minute chromosomes are cytogenetic manifestations of gene amplification frequently seen in cancer cells. Genes amplified on double minute chromosomes include oncogenes and multi-drug resistant genes. These genes encode proteins which contribute to cancer formation, cancer progression, and development of resistance to drugs used in cancer treatment. Elimination of double minute chromosomes, and therefore genes amplified on them, is an effective way to decrease the malignancy of cancer cells. We investigated the effectiveness of a cancer drug, gemcitabine, on the loss of double minute chromosomes from the ovarian cancer cell line UACC-1598. Gemcitabine is able to decrease the number of double minute chromosomes in cells at a 7500X lower concentration than the commonly used cancer drug hydroxyurea. Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment. Gemcitabine, even at a low nanomolar concentration, is able to cause DNA damage. The selective incorporation of double minutes chromatin and γ-H2AX signals into micronuclei provides a strong link between DNA damage and the loss of double minute chromosomes from gemcitabine treated cells. Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion. Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.
authors.affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Lisa
authors.initials: L
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Rongwei
authors.initials: R
authors.lastname: Guan
authors.forename: Donglin
authors.initials: D
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiangning
authors.initials: X
authors.lastname: Meng
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Wenjing
authors.initials: W
authors.lastname: Sun
authors.forename: Songbin
authors.initials: S
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005784:Gene Amplification / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010448:Peptide Initiation Factors / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000093542:Gemcitabine; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003841:Deoxycytidine; D006657:Histones; D006918:Hydroxyurea; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000093542:Gemcitabine; D000097574:Eukaryotic Translation Initiation Factor 5A; C468783:H2AX protein, human; C579095:MCL1 protein, human; C459801:MYCN protein, human