Quercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressions.
Nasopharyngeal carcinoma is a common cancer in South-East Asia, especially among people of Chinese origin. In this report, we investigate the effects of quercetin on the growth of wild-type and mutant p53 nasopharyngeal carcinoma cell lines, HK1 and CNE2 respectively. The wild-type p53 HK1 was more susceptible to growth inhibition by quercetin than the mutant p53 CNE2. The ID50 values for HK1 and CNE2 were 35.0 and 54.5 microM respectively. Cell growth arrest was initiated by the up-regulation of retinoblastoma gene expression, resulting in cell cycle arrest in either the G2/M or G0/G1 phase at 14.8 and 52.1 microM quercetin respectively regardless of the p53 status. Flow cytometry experiments revealed that quercetin-induced apoptosis during the first 24 h followed by necrosis in both HK1 and CNE2. Western blot experiments confirmed that cytotoxic killing of HK1 and CNE2 by quercetin was mediated by the up-regulation of pro-apoptotic protein Bad, caspase-3 and -7, resulting in cell death by apoptosis. Our study demonstrates that quercetin inhibits cell growth of nasopharyngeal carcinoma cell lines HK1 and CNE2 by inhibiting cell cycle progression to S phase. Quercetin is also able to induce apoptosis and necrosis in these cells regardless of the p53 status.
Ong
Chye Sun
CS
School of Chemical and Life Sciences, Singapore Polytechnic, Singapore 139651.
Tran
Evelyn
E
Nguyen
T T Tuyen
TT
Ong
Choon Kiat
CK
Lee
Siew Kuen
SK
Lee
Jia Jing
JJ
Ng
Chee Pang
CP
Leong
Caine
C
Huynh
Hung
H
D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy*; D002352:Carrier Proteins / Q000096:biosynthesis*; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009336:Necrosis; D010766:Phosphorylation; D011794:Quercetin / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000378:metabolism; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D051025:bcl-Associated Death Protein
C494819:BAD protein, human; D002352:Carrier Proteins; D004396:Coloring Agents; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein; D011794:Quercetin; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases