The (8-thiotheophyllinate) (triphenylphosphine) gold (I), (tTAuP): a new gold complex as an anticancer agent.
In continuous Friend leukemia cell exposure to tTAuP, the IC50 was 0.2 microM whereas in cells exposed 15 or 60 min to tTAuP followed by 72 h in drug-free medium the IC50 was 2.2 and 1.3 microM respectively. A combination of tTAuP and cisplatin (CDDP) is shown to be more active than either agent alone. Intracellular accumulation studies analysed by SXRF have shown that to achieve a cytotoxic effect, large concentrations of gold are necessary to accumulate in both the nuclear and cytoplasmic fraction. However, at cytostatic doses (1 microM), tTAuP has no effect on the cell cycle but does affect DNA synthesis. At a higher dose, greater than that necessary to induce cytotoxicity, it produces DNA damage, as observed by alkaline elution method. When cells were exposed to toxic doses of tTAuP (10 microM) in the presence of albumin, cytotoxicity was significantly reduced. Similar results were obtained when cells were co-treated with L-cysteine, dithiothreitol or reduced gluthatione. Reduced cytotoxic effect can be related to the interaction with free thiol groups. According to these data it is concluded that tTAuP is highly effective in vitro; whether it is active in vivo remains to be determined.
Garcia-Orad
A
A
Dpto de Biologia Celular, Universidad Pais Vasco, Leioa, Vizcaya, Spain.
Arizti
P
P
Sommer
F
F
Silvestro
L
L
Massiot
P
P
Chevallier
P
P
Gutierrez-Zorrilla
J M
JM
Colacio
E
E
Martinez de Pancorbo
M
M
Tapiero
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005622:Friend murine leukemia virus; D006046:Gold; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D006046:Gold; D002945:Cisplatin