Mechanism of cytotoxicity of turbinamide in vitro.
BACKGROUND
Previously, we demonstrated that turbinamide isolated from the marine ascidia Sydnium Turbinatum, exerts a selective cytotoxicity on glioma cells. Now we have investigated the mechanism of its cytotoxic effect on two different cell lines: C6 rat glioma cells and J774 murine monocyte/macrophages.


METHODS
Cell viability, membrane lipoperoxidation, DNA fragmentation and apoptosis were studied in C6 and J774 cells incubated with turbinamide for 24 hours.


RESULTS
Turbinamide (0.01-100 micrograms/ml) induced a dose-dependent inhibition of C6 cell viability (88.0 +/- 3.0%; 80.0 +/- 1.2%; 38.0 +/- 5.0%; 23.6 +/- 1.3% and 9.1 +/- 2.3%) with respect to the control (100% viability). Moreover, turbinamide (0.01-100 micrograms/ml) increased lipoperoxidation of C6 cells (1.21 +/- 0.11; 9.03 +/- 1.6; 17.8 +/- 1.6 and 45.03 +/- 1.01 ngMDA/1 x 10(6) cells) with respect to unstimulated cells (0.6 +/- 0.1 ngMDA/1 x 10(6) cells) that was accompanied by DNA damage, having no effect on J774. Interestingly, turbinamide (0.1-100 micrograms/ml) induced apoptosis in C6 cells.


CONCLUSIONS
Our study showed that the selective cytotoxicity of turbinamide to C6 cells is due to apoptosis, suggesting that turbinamide may be useful in the therapy of glioma.
Esposito
Giuseppe
G
Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
Aiello
Anna
A
Carbonelli
Sabina
S
Menna
Marialuisa
M
Fattorusso
Ernesto
E
Iuvone
Teresa
T
D000473:Alkanes / Q000494:pharmacology* / Q000633:toxicity; D000577:Amides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051381:Rats; D014407:Tumor Cells, Cultured
D000473:Alkanes; D000577:Amides; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C449319:turbinamide; D004247:DNA