Scutellarin sensitizes drug-evoked colon cancer cell apoptosis through enhanced caspase-6 activation.
BACKGROUND
We have reported that resveratrol (RSV) and 5-fluorouracil (5-FU) evoked apoptosis through caspase-6 activation in wild-type (p53+/+) and knockout (p53(-/-)) HCT116 human colon cancer cells. In this study, we investigated the sensitization effects of scutellarin (SC), a compound isolated from the traditional Chinese herb Erigeron breviscapus, on RSV and 5-FU-evoked apoptosis of these cancer cells.


METHODS
The drug-induced apoptosis was qualified by TUNEL staining under fluorescence microscopy, before being quantified by propiodium iodide staining through flow cytometric assay.


RESULTS
SC (100 microM) sensitized RSV- (200 microM) and 5-FU (500 microM)-evoked apoptosis in p53+/+ but not p53(-/-) cells. RSV- and 5-FU-elicited caspase-6 activation was promoted by SC in a time-dependent manner. SC itself did not trigger apoptosis or caspase-6 activation at the concentration tested.


CONCLUSIONS
SC is a novel sensitizing agent for both RSV- and 5-FU-evoked apoptosis, through the enhancement of caspase-6 activation in a p53-dependent manner.
Chan
Jason Yongsheng
JY
National University Medical Institutes, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. lee_shao@hotmail.com
Tan
Benny Kwong Huat
BK
Lee
Shao Chin
SC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053178:Caspase 6 / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004359:Drug Therapy, Combination; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage; D005965:Glucuronates / Q000494:pharmacology*; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D005965:Glucuronates; D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C484876:scutellarin; D047310:Apigenin; D053178:Caspase 6; D000077185:Resveratrol; D005472:Fluorouracil