Dorit[a]
J Neurooncol 2002 Nov;60(2):109-16
Chemosensitivity of glioblastoma cells during treatment with the organo-tin compound triethyltin(IV)lupinylsulfide hydrochloride.
Barbieri F, Sparatore F, Bonavia R, Bruzzo C, Schettini G, Alama A.
Laboratory of Pharmacology and Neuroscience, National Institute for Cancer Research, Advanced Biotechnology Center, Genoa, Italy.
Malignant gliomas are the most common primary brain tumors in humans. However, poor response to conventional therapeutic approaches, including chemotherapy, leads invariably to disease recurrence and progression. The organo-tin derivative triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29) was identified and developed as potential antiproliferative agent in human cancer cell lines. However, for its peculiar chemical structure and good lipophilicity, this compound also appeared an eligible candidate for the treatment of gliobastoma cells. The present experiments were designed to explore the in vitro effects of IST-FS 29 on four human glioblastoma cell lines: A-172, DBTRG.05MG, U-87MG and CAS-1. The average IC50 values were obtained by MTT assay and ranged between 3 and 10 microM. Time-course assays with cell recovery after drug withdrawal, demonstrated marked cytotoxicity following exposure to IST-FS 29 for 8, 24 and 72 h. Cultures treated for 8 h were able to partially re-grow by 144 h; on the contrary, longer times of exposure did not allow surviving cells to recover from the damage and actively proliferate. Cell morphology of cultures exposed to IST-FS 29 was assessed by inverted light microscopy after 24 and 72 h and was more consistent with cell death by necrosis which included cell size reduction, vacuolation of cytoplasm, round dying cells. The present results and our previous data, in vitro and in vivo, indicate the relevant cytotoxic activity of this organo-tin compound and suggest that IST-FS 29 might be a promising novel agent to be developed for the treatment of malignant brain neoplasms.