(-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells.
OBJECTIVE
Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells.


METHODS
The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis.


RESULTS
EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased.


CONCLUSIONS
Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.
Tang
Guo-Qing
GQ
Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, 100044, Beijing, China.
Yan
Tai-Qiang
TQ
Guo
Wei
W
Ren
Ting-Ting
TT
Peng
Chang-Liang
CL
Zhao
Hui
H
Lu
Xin-Chang
XC
Zhao
Fu-Long
FL
Han
Xiaoguang
X
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000473:pathology; D017931:DNA Primers; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics
D016588:Anticarcinogenic Agents; D017931:DNA Primers; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D002392:Catechin; C045651:epigallocatechin gallate