In vitro and in vivo anti-tumour activities of echinoside A and ds-echinoside A from Pearsonothuria graeffei.
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 G₀/G₁ 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 D₁. Western blotting analysis demonstrated that they down-regulated the expression of Bcl-2, and enhanced mitochondria 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.


CONCLUSIONS
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.
College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province, China.
Qin
Q
Zhao
Yong
Y
Xue
Jing-feng
JF
Wang
Hui
H
Li
Teng-teng
TT
Long
Zhaojie
Z
Li
Yu-ming
YM
Wang
Ping
P
Dong
Chang-hu
CH
Xue
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006697:Holothurin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D012616:Sea Cucumbers / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D006697:Holothurin; C048552:echinoside B; C043973:echinoside A