Apoptosis-inducing vanadocene compounds against human testicular cancer.
We systematically assessed the cytotoxic effects of five metallocene dichlorides containing vanadium (vanadocene dichloride), titanium (titanocene dichloride), zirconium (zircodocene dichloride), molybdenum (molybdocene dichloride), and hafnium (hafnocene dichloride) as the central metal atom and 19 other vanadocene complexes. These compounds were tested against the human testicular cancer cell lines Tera-2 and Ntera-2 using both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and apoptosis assays. Notably, only the vanadium(IV)-containing metallocenes exhibited significant cytotoxicity against Tera-2 and Ntera-2 cells and induced apoptosis within 24 h. Vanadocenes with dithiocyanate [VCp2(SCN)2 x 0.5 H2O] and diselenocyanate [VCp2(NCSe)2] as ancillary ligands were identified as the most potent cytotoxic compounds. Vanadocenes, especially the lead compound VCp2(NCSe)2, may be useful in the treatment of testicular cancer.
Ghosh
P
P
Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota 55113, USA.
D'Cruz
O J
OJ
Narla
R K
RK
Uckun
F M
FM
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D017968:Vanadium Compounds / Q000737:chemistry / Q000494:pharmacology*
D009942:Organometallic Compounds; D017968:Vanadium Compounds; D004247:DNA