EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells.
The anticarcinogenic actions of epigallocatechin-3-gallate (EGCG), one of the main ingredients of green tea, against various cancer types including cervical cancer are well documented. Studies pertaining to the exact molecular mechanism by which EGCG induces cancer cell growth inhibition needs to be investigated extensively. In the present study, we observed a stupendous dose dependent reduction in the protein expression of Fused Toes Homolog (FTS) after treatment with EGCG at 1, 10, 25 and 50 μM. Further, we were interested in finding out whether the decrease in the protein expression of FTS was due to decreased mRNA synthesis. Real time reverse transcriptase polymerase chain reaction results revealed a similar dose dependent reduction in the FTS mRNA after EGCG treatment. Chromatin immunoprecipitation analysis revealed the interaction between p53 and the promoter region of FTS. A dose dependent increase in this interaction was evidenced at 25 and 50 μM EGCG treatment. p53 silencing increased the expression of FTS and also decreased the reduction in the levels of FTS expression after EGCG treatment. The decrease in the levels of FTS was more significant at 25 and 50 μM and is associated with reduced physical interaction of FTS with Akt, phosphorylation of Akt and survival of HeLa cells. Collectively, these results conclude that EGCG induced anti-proliferative action in the cervical cancer cell involves reduced mRNA expression of FTS through p53.
Department of Radiation Oncology, College of Medicine, Chungbuk National University, Cheongju, 361-763, South Korea.
Sridhar
S
Muthusami
D S
DS
Prabakaran
Zhengzhe
Z
An
Jae-Ran
JR
Yu
Woo-Yoon
WY
Park
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt