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Title of Journal: Apoptosis

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Abbravation: Apoptosis

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Springer US

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DOI

10.1002/chin.199209229

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ISSN

1573-675X

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Shogaols at proapoptotic concentrations induce GS

Authors: FeiFei Gan Amrita A Nagle Xiaohui Ang Olivia Huixian Ho SockHoon Tan Hong Yang WaiKeung Chui EngHui Chew
Publish Date: 2011/05/20
Volume: 16, Issue: 8, Pages: 856-867
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Abstract

Shogaols have been previously reported to induce cancer cell death via multiple mechanisms among which one analog 6shogaol 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 10shogaol was synthesized and evaluated for antiproliferative activity in HCT 116 colon carcinoma and SHSY5Y neuroblastoma cells 4 and 6shogaol were identified as lead compounds possessing the strongest antiproliferative activity In the soft agar assay the lead shogaols displayed dosedependent inhibition on cancer cell colony formation under anchorageindependent conditions Using HCT 116 as the selected cancer cell line the molecular events linking shogaolsinduced 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 6shogaol induced irreversible G2/M arrest that was at least in part associated with downregulation of cell cycle checkpoint proteins cdk1 cyclin B and cdc25C as well as spindle assembly checkpoint proteins mad2 cdc20 and survivin A dose and timedependent 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

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  9. Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomal-mitochondrial axis
  10. The c-Abl tyrosine kinase stabilizes Pitx1 in the apoptotic response to DNA damage
  11. Ouabain-induced apoptosis and Rho kinase: a novel caspase-2 cleavage site and fragment of Rock-2
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  15. Nitrate tolerance aggravates postischemic myocardial apoptosis and impairs cardiac functional recovery after ischemia
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  23. Inducer-and cell type-specific regulation of antiapoptotic MCL1 in myeloid leukemia and multiple myeloma cells exposed to differentiation-inducing or microtubule-disrupting agents
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