Proteomic profiling revealed the functional networks associated with mitotic catastrophe of HepG2 hepatoma cells induced by 6-bromine-5-hydroxy-4-methoxybenzaldehyde

Bo Zhang, Bo Huang, Hua Guan, Shi Meng Zhang, Qin Zhi Xu, Xing Peng He, Xiao Dan Liu, Yu Wang, Zeng Fu Shang, Ping Kun Zhou

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Mitotic catastrophe, a form of cell death resulting from abnormal mitosis, is a cytotoxic death pathway as well as an appealing mechanistic strategy for the development of anti-cancer drugs. In this study, 6-bromine-5-hydroxy-4-methoxybenzaldehyde was demonstrated to induce DNA double-strand break, multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human hepatoma HepG2 cells. We used proteomic profiling to identify the differentially expressed proteins underlying mitotic catastrophe. A total of 137 differentially expressed proteins (76 upregulated and 61 downregulated proteins) were identified. Some of the changed proteins have previously been associated with mitotic catastrophe, such as DNA-PKcs, FoxM1, RCC1, cyclin E, PLK1-pT210, 14-3-3? and HSP70. Multiple isoforms of 14-3-3, heat-shock proteins and tubulin were upregulated. Analysis of functional significance revealed that the 14-3-3-mediated signaling network was the most significantly enriched for the differentially expressed proteins. The modulated proteins were found to be involved in macromolecule complex assembly, cell death, cell cycle, chromatin remodeling and DNA repair, tubulin and cytoskeletal organization. These findings revealed the overall molecular events and functional signaling networks associated with spindle disruption and mitotic catastrophe.

Original languageEnglish (US)
Pages (from-to)307-317
Number of pages11
JournalToxicology and Applied Pharmacology
Volume252
Issue number3
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Cell cycle arrest
  • DNA damage
  • Microtubule
  • Mitotic catastrophe
  • Spindle assembly
  • Therapeutic target
  • Vanillin derivative

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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