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: Lisa Yu, Yan Zhao, Chao Quan, Wei Ji, Jing Zhu, Yun Huang, Rongwei Guan, Donglin Sun, Yan Jin, Xiangning Meng, Chunyu Zhang, Yang Yu, Jing Bai, Wenjing Sun, Songbin Fu
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e71988 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23991020 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA, Neoplasm
• H2AX protein, human
• Histones
• MCL1 protein, human
• MYCN protein, human
• Myeloid Cell Leukemia Sequence 1 Protein
• N-Myc Proto-Oncogene Protein
• Nuclear Proteins
• Oncogene Proteins
• Peptide Initiation Factors
• RNA-Binding Proteins
• eukaryotic translation initiation factor 5A
• Deoxycytidine
• Hydroxyurea
• Gemcitabine

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Damage (drug effects)
• DNA, Neoplasm (genetics, metabolism)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Female
• Gene Amplification (drug effects)
• Histones (metabolism)
• Humans
• Hydroxyurea (pharmacology)
• In Situ Hybridization, Fluorescence
• Micronuclei, Chromosome-Defective (drug effects)
• Myeloid Cell Leukemia Sequence 1 Protein (genetics)
• N-Myc Proto-Oncogene Protein
• Nuclear Proteins (genetics)
• Oncogene Proteins (genetics)
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Peptide Initiation Factors (genetics)
• RNA-Binding Proteins (genetics)
• Real-Time Polymerase Chain Reaction
• Gemcitabine