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

8 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