Cytotoxic Effects of a Triorganotin Derivative on HTLV-1-Infected Cells at Different Immortalization/Transformation Stages In Vitro

TL;DR

This study shows that a tin-based compound has strong cytotoxic effects on HTLV-1-infected cells in different transformation stages, suggesting potential as an anti-cancer agent.

Contribution

The study is the first to demonstrate the cytotoxic effects of a tin-based compound on HTLV-1-infected cells at various transformation stages.

Findings

TBT induced dose-dependent inhibition of metabolic activity and viability in HTLV-1-infected cells.

Apoptotic cell death was involved in the cytotoxic effects of TBT, though other forms of cell death may also be involved.

C91/PL cells showed resistance to TBT, indicating cell-type-dependent effects.

Abstract

Among the metal-derived complexes, recently, tin derivatives have been investigated as promising anti-cancer drug candidates. Our previous study showed that the tin-based compound Bu3SnOCOCF3 (TBT) exerts cytotoxic activity on solid tumor cell lines. In the present study, the effects of TBT were evaluated in vitro on HTLV-1-infected human lymphocytic cell lines at different stages of viral transformation, consisting of IL-2-dependent (PB2/IL-2) and IL-2-independent (PB2/NO-IL-2) cells, generated in our laboratory by HTLV-1 in vitro infection of lymphocytes from the same donor, and the C91/PL cell line established by co-cultivation with T cells from a patient with HTLV-1-positive leukemia. TBT induced a reliable and reproducible dose-dependent inhibition of metabolic activity and viability in the HTLV-1-infected cells. The effect was cell-type-dependent, with C91/PL cells being quite resistant. An investigation into the cytotoxic effects induced by TBT in HTLV-1-infected cells and data on caspase inhibitors/caspase activation indicated that apoptotic cell death was involved, but also that the possible involvement of other forms of cell death could not be excluded. Taken together, the results show for the first time that the tin-based compound, although not devoid of a certain cytotoxicity toward uninfected cells, can induce typical and potent effects on HTLV-1-infected cells.

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