Genistein induces growth inhibition and G2/M arrest in nasopharyngeal carcinoma cells.
Nasopharyngeal carcinoma (NPC) is an endemic malignant disease of the head and neck region with unique features including striking ethnic and geographic variations as well as multifactorial etiology. Previous studies have demonstrated the anticancer properties of genistein, the major soy isoflavonoid, in several human cancer cells such as breast, prostate, colon, gastric, lung, and hepatoma. However, the action of genistein in NPC cells has not been determined. In this study, we investigated the inhibitory effects of genistein on NPC cells and its possible underlying mechanisms. We found that genistein dose-dependently inhibited the proliferation of human NPC cell line CNE2 cells. DNA flow cytometric analysis revealed that 30 to 120 microM genistein induced dramatic G2/M phase arrest in NPC cells. The mRNA expression levels, as shown by gene expression array and quantitative real-time polymerase chain reaction, and the protein expression levels of the cell cycle regulators p21(Cip1) and ATR (Ataxia telangiectasia and Rad3 related) were elevated following genistein treatment. Interestingly, we also observed concomitant induction of p15(Ink4b) in genistein induced inhibitory effects in NPC cells. Moreover, selective estrogen receptor modulators did not affect genistein induced growth inhibition. These findings provide new insights into the potential intervention of NPC with genistein.
Han
Hongyu
H
Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Zhong
Caiyun
C
Zhang
Xuchao
X
Liu
Ranyi
R
Pan
Meixia
M
Tan
Li
L
Li
Yan
Y
Wu
Jiangxue
J
Zhu
Yinghui
Y
Huang
Wenlin
W
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004032:Diet; D016195:G2 Phase / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology
D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011960:Receptors, Estrogen; D019833:Genistein; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases