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  • Title: 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.
    Author: Park C, Kim GY, Kim WI, Hong SH, Park DI, Kim ND, Bae SJ, Jung JH, Choi YH.
    Journal: Chemotherapy; 2007; 53(3):160-8. PubMed ID: 17356266.
    Abstract:
    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.
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