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

Journal Article · Sun May 01 04:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.03.003· OSTI ID:21535289

Bo, Zhang ^[1]; Bo, Huang ^[1]; Hua, Guan; Shimeng, Zhang; Qinzhi, Xu ^[1]; Xingpeng, He ^[2]; Xiaodan, Liu; Yu, Wang; Zengfu, Shang ^[1]

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1. Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)
2. School of Public Health, University of South China, Hengyang, Hunan 421001 (China)

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{sigma} 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. - Graphical abstract: Display Omitted Research highlights: > 6-bromoisovanillin induced spindle disruption and sustained mitotic arrest, consequently resulted in mitotic catastrophe. > Proteomic profiling identified 137 differentially expressed proteins associated mitotic catastrophe. > The 14-3-3-mediated signaling network was the most significantly enriched for the altered proteins. > The macromolecule complex assembly, cell cycle, chromatin remodeling and DNA repair, tubulin organization were also shown involved in mitotic catastrophe.

• OSTI ID: 21535289
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 252; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BROMINE
CELL CONSTITUENTS
CELL CYCLE
CELL DIVISION
CHROMATIN
DEATH
DNA
DNA DAMAGES
DNA REPAIR
DRUGS
ELEMENTS
HALOGENS
HEAT-SHOCK PROTEINS
HUMAN POPULATIONS
MICROTUBULES
MITOSIS
NONMETALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POPULATIONS
PROTEINS
REPAIR
STRAND BREAKS