EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression.
EGCG (epigallocatechin gallate), the major catechin found in green tea, has been shown to inhibit proliferation and induce apoptosis in many tumors. EGCG can inhibit DNMT (DNA methyltransferase) activity, and cause CpG demethylation and reactivation of methylation-silenced genes. Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type serine proteinase inhibitor family, is inversely related to an increasing degree of malignancy. Our previous study showed that the expression of TFPI-2 and invasiveness of renal cell carcinoma had a negative correlation. Overexpression of TFPI-2 may induce tumor cell apoptosis in renal cell carcinoma. Lower expression of TFPI-2 in renal cell carcinoma was partly due to hypermethylation of the gene promoter. Herein, using MTT and flow cytometry, we demonstrated that EGCG can inhibit growth and induces apoptosis in renal cell carcinoma cell line 786-0. In addition, Western blotting and real-time RT-PCR showed that EGCG can upregulate expression of TFPI-2. Before and after EGCG treatment, real-time methylation specific PCR could not detect methylation status of TFPI-2 gene promoter in cell line 786-0. In vivo invasiveness and metastasis test did not indicate any significant differences between control and treatment group. Our results suggest that EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. This is the first report showing that EGCG is likely to be an effective agent for renal cell carcinoma.
Gu
Bin
B
Department of Urology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China.
Ding
Qiang
Q
Xia
Guowei
G
Fang
Zujun
Z
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2; D002392:Catechin; C045651:epigallocatechin gallate