Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

Jeong Eun Park, Seon Rang Woo, Chang Mo Kang, Kyoung Mi Juhn, Yeun Jin Ju, Hyun Jin Shin, Hyun Yoo Joo, Eun Ran Park, In chul Park, Sung Hee Hong, Sang Gu Hwang, Jung Kee Lee, Hae Kwon Kim, Myung Haing Cho, Gil Hong Park, Kee Ho Lee

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

    Original languageEnglish
    Pages (from-to)615-621
    Number of pages7
    JournalBiochemical and biophysical research communications
    Volume404
    Issue number2
    DOIs
    Publication statusPublished - 2011 Jan 14

    Keywords

    • Chromosomal end-to-end fusion
    • Multinucleation
    • Paclitaxel
    • Telomere

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization'. Together they form a unique fingerprint.

    Cite this