Please use this identifier to cite or link to this item: https://doi.org/10.1007/s10495-011-0611-3
Title: Shogaols at proapoptotic concentrations induce G2/M arrest and aberrant mitotic cell death associated with tubulin aggregation
Authors: Gan, F.-F. 
Nagle, A.A.
Ang, X.
Ho, O.H.
Tan, S.-H.
Yang, H.
Chui, W.-K. 
Chew, E.-H. 
Keywords: Apoptosis
Cell cycle checkpoint proteins
G2/M arrest
Shogaols
Spindle assembly checkpoint proteins
Tubulin
Issue Date: Aug-2011
Source: Gan, F.-F., Nagle, A.A., Ang, X., Ho, O.H., Tan, S.-H., Yang, H., Chui, W.-K., Chew, E.-H. (2011-08). Shogaols at proapoptotic concentrations induce G2/M arrest and aberrant mitotic cell death associated with tubulin aggregation. Apoptosis 16 (8) : 856-867. ScholarBank@NUS Repository. https://doi.org/10.1007/s10495-011-0611-3
Abstract: Shogaols have been previously reported to induce cancer cell death via multiple mechanisms, among which one analog 6-shogaol has been reported to cause microtubule damage through specific reaction with sulfhydryl groups in tubulin. In this study, a series of shogaols with different side chain lengths (4-, 6-, 8- and 10-shogaol) was synthesized and evaluated for antiproliferative activity in HCT 116 colon carcinoma and SH-SY5Y neuroblastoma cells. 4- and 6-shogaol were identified as lead compounds possessing the strongest antiproliferative activity. In the soft agar assay, the lead shogaols displayed dose-dependent inhibition on cancer cell colony formation under anchorage-independent conditions. Using HCT 116 as the selected cancer cell line, the molecular events linking shogaols-induced G2/M cell cycle arrest to apoptosis characterized by caspase 3 and PARP cleavage were investigated. At sublethal concentrations, the halt at G2/M phase was alleviated along time and cells survived. Conversely, proapoptotic concentrations of 4- and 6-shogaol induced irreversible G2/M arrest that was at least in part associated with down-regulation of cell cycle checkpoint proteins cdk1, cyclin B and cdc25C, as well as spindle assembly checkpoint proteins mad2, cdc20 and survivin. A dose- and time-dependent accumulation of insoluble tubulin in the insoluble fractions of cell lysates provided evidence that G2 checkpoint failure led to disruption of microtubule turnover. In summary, our results conclude that shogaols cause apoptosis by inducing aberrant mitosis at least through the attenuation of cell cycle and spindle assembly checkpoint proteins. © 2011 Springer Science+Business Media, LLC.
Source Title: Apoptosis
URI: http://scholarbank.nus.edu.sg/handle/10635/106331
ISSN: 13608185
DOI: 10.1007/s10495-011-0611-3
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

26
checked on Feb 15, 2018

WEB OF SCIENCETM
Citations

22
checked on Feb 5, 2018

Page view(s)

29
checked on Feb 20, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.