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In vitro and in vivo anti‐tumour activities of echinoside A and ds ‐echinoside A from Pearsonothuria graeffei
Author(s) -
Zhao Qin,
Xue Yong,
Wang Jingfeng,
Li Hui,
Long Tengteng,
Li Zhaojie,
Wang Yuming,
Dong Ping,
Xue Changhu
Publication year - 2011
Publication title -
journal of the science of food and agriculture
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 142
eISSN - 1097-0010
pISSN - 0022-5142
DOI - 10.1002/jsfa.4678
Subject(s) - in vivo , in vitro , chemistry , biology , psychology , biochemistry , genetics
BACKGROUND: Echinoside A (EA) and ds ‐echinoside A (DSEA) are triterpene glycosides isolated from the sea cucumber Pearsonothuria graeffei . DSEA, the desulfurisation product of EA, has the following structure: β‐ D ‐xylopyranosyl‐holost‐8(9),11(12)‐diene‐3β,17α‐diol. In the present study, we examined the anti‐tumour activities—in particular, the structure‐activity relationships—of EA and DSEA in vitro and in vivo . RESULTS: Both EA and DSEA exhibited an inhibitory effect on cell proliferation, along with apoptosis‐inducing activity, in HepG2 cells. Moreover, they significantly arrested the cell cycle in the G 0 /G 1 phase. A reverse transcriptase‐polymerase chain reaction assay revealed that EA and DSEA significantly increased the expression of the cell‐cycle‐related genes, namely, p16, p21 and c‐myc , and decreased that of cyclin D 1 . Western blotting analysis demonstrated that they down‐regulated the expression of Bcl‐2 , and enhanced mitochondrial cytochrome c release, caspase‐3 activation, and poly(adenosine diphosphate ribose) polymerase, cleavage. Nuclear factor kappa B (NF‐κB) expression was significantly decreased by DSEA, but was unaffected by EA. EA and DSEA (2.5 mg kg −1 ) treatment of mice bearing H22 hepatocarcinoma tumours reduced the tumour weight by 49.8% and 55.0%, respectively. CONCLUSION: EA and DSEA exhibit marked anti‐cancer activity in HepG2 cells, by blocking cell‐cycle progression and inducing apoptosis through the mitochondrial pathway. DSEA‐induced apoptosis was more potent than EA‐induced apoptosis. Furthermore, the two triterpene glycosides derived from P. graeffei may induce apoptosis of HepG2 cells in an NF‐κB‐dependent or NF‐κB‐independent manner, depending on their structure. Copyright © 2011 Society of Chemical Industry