Spontaneous and 5-fluorouracil-induced centrosome amplification lowers the threshold to resveratrol-evoked apoptosis in colon cancer cells.
We recently reported that caspase-6 activation is a major molecular event underlying resveratrol-triggered apoptosis in HCT116 colon cancer cells with or without p53. In the present study, we investigated the relationship between centrosome amplification and apoptosis sensitivity in cancer cells. We found that centrosome amplification, which occurs spontaneously in cancer cells, could be induced by a subtoxic concentration of 5-fluorouracil. Cancer cells with centrosome amplification, either spontaneous or 5-fluorouracil-induced, were more sensitive to apoptosis induction by resveratrol. In cancer cells, a subtoxic concentration of 5-fluorouracil also enhanced resveratrol-evoked caspase-6 activation. Functional loss of p53 promoted spontaneous, not 5-fluorouracil-induced, centrosome amplification. We conclude that centrosome amplification, either spontaneous or 5-fluorouracil-induced, confers higher apoptosis sensitivity to cancer cells. Drug induction of centrosome amplification might be a novel chemosensitization approach to cancer therapy.
Lee
Shao Chin
SC
National University Medical Institute, National University of Singapore, Singapore. lee_shao@hotmail.com
Chan
Jason Yongsheng
JY
Pervaiz
Shazib
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053178:Caspase 6 / Q000378:metabolism; D018385:Centrosome / Q000187:drug effects* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C505514:CASP6 protein, human; D053178:Caspase 6; D000077185:Resveratrol; D005472:Fluorouracil