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Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells.

Yu L, Zhao Y, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, Fu S - PLoS ONE (2013)

Bottom Line: Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

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.

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Related in: MedlinePlus

HU and GEM treatment decreases the number of DMs in UACC-1598.A. Representative pictures of metaphase spread of UACC-1598 and UACC-1598-4 cells. Arrows indicate DMs. The number of DMs in each metaphase cell was counted and plotted. ***indicates P<0.001. B. Metaphase spreads were prepared for cells grown in the presence of low concentrations of either HU or GEM for 1 week or 2 weeks. The number of DMs in each metaphase cell was counted. The red lines represent the mean and the black lines represent the SEM. *denotes a P value of 0.01 to 0.05 and **denotes a P value of 0.001 to 0.01.
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pone-0071988-g001: HU and GEM treatment decreases the number of DMs in UACC-1598.A. Representative pictures of metaphase spread of UACC-1598 and UACC-1598-4 cells. Arrows indicate DMs. The number of DMs in each metaphase cell was counted and plotted. ***indicates P<0.001. B. Metaphase spreads were prepared for cells grown in the presence of low concentrations of either HU or GEM for 1 week or 2 weeks. The number of DMs in each metaphase cell was counted. The red lines represent the mean and the black lines represent the SEM. *denotes a P value of 0.01 to 0.05 and **denotes a P value of 0.001 to 0.01.

Mentions: UACC-1598 is an ovarian cancer cell line consisting of gene amplification in the form of DMs. UACC-1598-4 was created by the serial dilution method by seeding and isolating single cells from the parental cell line UACC-1598 and preparing metaphase spreads to determine the number of DMs a clone contains. This clone was found to have an increase in the number of DMs when compared with the parental cell line (Figure 1A). While the UACC-1598 cell line contained an average of 34.61 DMs per cell, UACC-1598-4 had an average of 76.16 DMs per cell which is more than double the value for the parental cell line. The difference between the number of DMs in UACC-1598 and the clone UACC-1598-4 were found to be statistically significant with a P value of <0.001.


Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells.

Yu L, Zhao Y, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, Fu S - PLoS ONE (2013)

HU and GEM treatment decreases the number of DMs in UACC-1598.A. Representative pictures of metaphase spread of UACC-1598 and UACC-1598-4 cells. Arrows indicate DMs. The number of DMs in each metaphase cell was counted and plotted. ***indicates P<0.001. B. Metaphase spreads were prepared for cells grown in the presence of low concentrations of either HU or GEM for 1 week or 2 weeks. The number of DMs in each metaphase cell was counted. The red lines represent the mean and the black lines represent the SEM. *denotes a P value of 0.01 to 0.05 and **denotes a P value of 0.001 to 0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750019&req=5

pone-0071988-g001: HU and GEM treatment decreases the number of DMs in UACC-1598.A. Representative pictures of metaphase spread of UACC-1598 and UACC-1598-4 cells. Arrows indicate DMs. The number of DMs in each metaphase cell was counted and plotted. ***indicates P<0.001. B. Metaphase spreads were prepared for cells grown in the presence of low concentrations of either HU or GEM for 1 week or 2 weeks. The number of DMs in each metaphase cell was counted. The red lines represent the mean and the black lines represent the SEM. *denotes a P value of 0.01 to 0.05 and **denotes a P value of 0.001 to 0.01.
Mentions: UACC-1598 is an ovarian cancer cell line consisting of gene amplification in the form of DMs. UACC-1598-4 was created by the serial dilution method by seeding and isolating single cells from the parental cell line UACC-1598 and preparing metaphase spreads to determine the number of DMs a clone contains. This clone was found to have an increase in the number of DMs when compared with the parental cell line (Figure 1A). While the UACC-1598 cell line contained an average of 34.61 DMs per cell, UACC-1598-4 had an average of 76.16 DMs per cell which is more than double the value for the parental cell line. The difference between the number of DMs in UACC-1598 and the clone UACC-1598-4 were found to be statistically significant with a P value of <0.001.

Bottom Line: Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

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.

Show MeSH
Related in: MedlinePlus