The inhibitory effect of Gleditsia sinensis on cyclooxygenase-2 expression in human esophageal squamous cell carcinoma.
The anti-cancer effects of the anomalous fruit extract of Gleditsia sinensis (GSE) attributed to its apoptotic activity, telomerase inhibition and anti-angiogenesis in a panel of solid and non-solid tumor cell lines including esophageal squamous cell carcinoma (ESCC) have been intensively investigated by us in previous studies. Cyclooxygenase-2 (COX-2) has been well described as another promising target of cancer therapy for ESCC, and novel therapeutic agents are still being sought which target COX-2 expression. However, the anti-cancer effect of GSE through the suppression of COX-2 expression has not been previously investigated. In the present study, the anti-cancer effects of GSE on eight ESCC cell lines (KYSE 30, KYSE 150, KYSE 450, KYSE 510, KYSE 520, HKESC-3, HKESC-4 and SLMT-1) of Chinese and Japanese origins were first studied by MTS cytotoxicity assays. The effects of GSE on COX-2 expression levels and on the housekeeping form COX-1 were also investigated by multiplex RT-PCR analysis. Moreover, the anti-proliferative effect of GSE on KYSE 510 was also studied by anchorage-independent clonogenicity assay in soft agar. The results showed that GSE induced a dose- and time-dependent cytotoxicity on all of the eight ESCC cell lines and caused positive anti-proliferative action on KYSE 510 in the anchorage-independent clonogenicity assay, suggesting that GSE suppressed the in vitro growth of the ESCC cell lines. More importantly, the MRNA expression levels of COX-2, but not COX-1, in all of the ESCC cell lines were suppressed by GSE in a dose-dependent fashion. The overall results of the present study show that the anti-cancer effect of GSE on the ESCC cell lines is associated with the suppression of COX-2 expression, but not COX-1. Our findings also open a new chapter for the future advancement of GSE as a novel anti-cancer agent or as an adjuvant of traditional cancer treatments.
Pak
K C
KC
Lo Ka Chung Centre for Natural Anti-cancer Drug Development, The Hong Kong Polytechnic University, Hong Kong SAR, P.R. China.
Lam
K Y
KY
Law
S
S
Tang
J C O
JC
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003603:Cytotoxins / Q000302:isolation & purification / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation; D031501:Gleditsia / Q000737:chemistry*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D003603:Cytotoxins; D010936:Plant Extracts; D051546:Cyclooxygenase 2