Induction of apoptosis by (Z)-stellettic acid C, an acetylenic acid from the sponge Stelletta sp., is associated with inhibition of telomerase activity in human leukemic U937 cells.
BACKGROUND
(Z)-stellettic acid C, an acetylenic acid from the marine sponge Stelletta sp., has been shown to have cytotoxic activity in some cancer cells; however, its mechanisms on malignant cell growth are not known. In this study, the potential of (Z)-stellettic acid C to induce apoptosis in human leukemic U937 cells and its effects on telomerase activity were investigated.


METHODS
Cytotoxicity was evaluated by MTT assays. Apoptosis was detected using DAPI staining and annexin V fluorescein. The mRNAs of Bcl-2, inhibitor of apoptosis proteins (IAPs) family and Fas/FasL system were determined by RT-PCR. Caspases and telomerase activities were measured using colorimetric assay and telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA), respectively.


RESULTS
Exposure of U937 cells to (Z)-stellettic acid C resulted in growth inhibition and induction of apoptosis in a dose-dependent manner, which was associated with the modulation of Bcl-2 family expression, activation of caspases and downregulation of IAPs family members. (Z)-Stellettic acid C treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase, a main determinant of the telomerase enzymatic activity, was progressively downregulated by (Z)-stellettic acid C treatment.


CONCLUSIONS
These results suggest that (Z)-stellettic acid C could have a possible cancer therapeutic potential.
Park
Cheol
C
Department of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan, Korea.
Kim
Gi-Young
GY
Kim
Won Il
WI
Hong
Sang Hoon
SH
Park
Dong Il
DI
Kim
Nam Deuk
ND
Bae
Song-Ja
SJ
Jung
Jee H
JH
Choi
Yung Hyun
YH
D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D011161:Porifera / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D000077022:Survivin; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
D000480:Alkynes; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D005231:Fatty Acids, Unsaturated; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; C031203:2-hexadecynoic acid; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9