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.

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.

• Authors: Cheol Park, Gi-Young Kim, Won Il Kim, Sang Hoon Hong, Dong Il Park, Nam Deuk Kim, Song-Ja Bae, Jee H Jung, Yung Hyun Choi
• Journal: Chemotherapy (Chemotherapy) Vol. 53 Issue 3 Pg. 160-8 ( 2007) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 17356266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 S. Karger AG, Basel.

Chemical References

• Alkynes
• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• BIRC5 protein, human
• Fatty Acids, Unsaturated
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• Neoplasm Proteins
• RNA, Messenger
• Survivin
• 2-hexadecynoic acid
• TERT protein, human
• Telomerase
• Caspase 3
• Caspase 8
• Caspase 9

Topics

• Alkynes (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Proliferation (drug effects)
• Fatty Acids, Unsaturated (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins (genetics)
• Neoplasm Proteins (genetics)
• Porifera (chemistry)
• RNA, Messenger (metabolism)
• Survivin
• Telomerase (antagonists & inhibitors, genetics, metabolism)
• U937 Cells