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Bisphenol A disrupts mitotic progression via disturbing spindle attachment to kinetochore and centriole duplication in cancer cell lines
- Source :
- Toxicology in vitro : an international journal published in association with BIBRA. 59
- Publication Year :
- 2019
-
Abstract
- Bisphenol A [BPA, 2,2-bis-(4-hydroxyphenyl)propane] is one of the most prevalent synthetic environmental estrogens; as an endocrine disruptor, it is associated with endocrine-related cancers including breast, ovarian, and prostate. However, the mechanisms by which BPA contributes to carcinogenesis are unclear. This study aims to clarify its toxic effects on mitotic cells and investigate the molecular mechanism. In vitro effects of BPA on mitotic progression were examined by performing experiments on HeLa cells. Proteins involved in mitotic processes were detected by Western blot, live cell imaging, and immunofluorescence staining. The results showed that BPA increased chromosomal instability by perturbing mitotic processes such as bipolar spindle formation and spindle microtubule attachment to the kinetochore. BPA prolonged mitotic progression by disturbing spindle attachment and concomitant activating spindle assembly checkpoint (SAC). Mechanistically, BPA interfered proper localization of HURP to the proximal ends of spindle microtubules, Kif2a to the minus ends of spindle microtubules, and TPX2 on the mitotic spindle. This mislocalization of microtubule associated proteins (MAPs) is postulated to lead to spindle attachment failure. Furthermore, BPA caused multipolar spindle by inducing centriole overduplication and premature disengagement. Although BPA acts as an estrogen receptor (ER) agonist, mitotic defects caused by BPA occurred in an ER-independent manner. Our findings indicate that BPA may stimulate carcinogenesis not only by acting as an endocrine disruptor but also by increasing chromosomal instability during mitosis.
- Subjects :
- 0301 basic medicine
endocrine system
Centriole
Microtubule-associated protein
Carcinogenesis
Mitosis
Endocrine Disruptors
Toxicology
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Phenols
Chromosome instability
Chromosomal Instability
medicine
Humans
Benzhydryl Compounds
Kinetochores
Centrioles
urogenital system
Kinetochore
Chemistry
General Medicine
Cell biology
Spindle apparatus
Neoplasm Proteins
Spindle checkpoint
030104 developmental biology
030220 oncology & carcinogenesis
MCF-7 Cells
hormones, hormone substitutes, and hormone antagonists
HeLa Cells
Subjects
Details
- ISSN :
- 18793177
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Toxicology in vitro : an international journal published in association with BIBRA
- Accession number :
- edsair.doi.dedup.....de05df51e4ed10902ae88717d001ec24