Organotin compounds, particularly tri-organotin, have demonstrated cytotoxic properties against a number of tumor cell lines. On this basis,
triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), a
quinolizidine derivative, was synthesized and developed as a potential
antitumor agent. This
tin-derived compound exhibited potent antiproliferative effects on three different human
cancer cell lines:
teratocarcinoma of the ovary (PA-1), colon
carcinoma (HCT-8) and
glioblastoma (A-172). Cytotoxic activity was assessed by MTT and cell count assays during time course experiments with cell recovery after compound withdrawal. Significant cell growth inhibition (up to 95% in HCT-8 after 72 h of exposure), which also persisted after
drug-free medium change, was reported in all the cell lines by both assays. In addition, the cytocidal effects exerted by
IST-FS 29 appeared more consistent with
necrosis or delayed cell death, rather than apoptosis, as shown by morphologic observations under light microscope, DNA fragmentation analysis and flow cytometry. In the attempt to elucidate whether this compound might affect genes playing a role in G1/S phase transition, the expressions of p53, p21(WAF1),
cyclin D1 and Rb, mainly involved in response to
DNA-damaging stress, were analyzed by Western blot. Heterogeneous patterns of expression during exposure to
IST-FS 29 were evidenced in the different cell lines suggesting that these cell-cycle-related genes are not likely the primary targets of this compound. Thus, the present data seem more indicative of a direct effect of
IST-FS-29 on macromolecular synthesis and cellular homeostasis, as previously hypothesized for other organotin complexes.