Inhibitory effects of Gleditsia sinensis fruit extract on telomerase activity and oncogenic expression in human esophageal squamous cell carcinoma.
Previous studies have shown that the anomalous fruit extract of Gleditsia sinensis (GSE) exhibited apoptotic properties in various solid and non-solid tumors in vitro. However, the inhibitory actions of GSE on oncogenic expression and telomerase activity in esophageal squamous cell carcinoma (ESCC) have not been studied before. In the present study, the anti-cancer effects of GSE were demonstrated in three ESCC cell lines (HKESC-1, HKESC-2 and SLMT-1) by MTS and anchorage-independent clongen-icity assays, expression studies on oncogenes at 11q13 (CCND1, INT2, FGF4 and EMS1) and real-time quantitative telomeric repeat amplification protocol assay to show the inhibitory effect of GSE on telomerase in ESCC. The means of MTS50 of GSE for the ESCC cell lines and non-tumor NIH 3T3 cells were 21 and 163 microg/ml respectively. The anchorage-independent clongenicity assay showed that SLMT-1 cells lost their colony-forming potential which was dose-dependent to GSE. Moreover, GSE demonstrated dose-dependent suppression on the expression of INT2, EMS1 and FGF4, and inhibition of telomerase activity in the ESCC cell lines. Our overall results thus provide the first evidence that the anti-cancer effects of GSE on ESCC involve the suppression of oncogenic expression and inhibition of telomerase activity. Our findings also offer a new opportunity for the future development of GSE as a novel anti-cancer agent for ESCC and possibly for other cancers.
Tang
Wing K
WK
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, P.R. China.
Chui
Chung H
CH
Fatima
Sarwat
S
Kok
Stanton H L
SH
Pak
Kai C
KC
Ou
Tian M
TM
Hui
Kin S
KS
Wong
Mei M
MM
Wong
John
J
Law
Simon
S
Tsao
S W
SW
Lam
King Y
KY
Beh
Philip S L
PS
Srivastava
Gopesh
G
Ho
Kwok P
KP
Chan
Albert S C
AS
Tang
Johnny C O
JC
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005638:Fruit / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D031501:Gleditsia / Q000737:chemistry; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019098:Telomerase