Metal-Based Anticancer Agents: In vitro DNA Binding, Cleavage and Cytotoxicity

Two new metal-based anticancer chemotherapeutic agents, [(Ph2Sn)2(HGuO)2(phen)Cl2] 1 and [(Ph3Sn)(HGuO)(phen)]- Cl.CH3OH.H2O 2, were designed, prepared and characterized by analytical and spectral (IR, ESI-Mass, 1H, 13C and 119Sn NMR) techniques. The proposed geometry of Sn(IV) in 1 and 2 is distorted octahedral and distorted trigonal-bipyramidal, respectively. Both 1 and 2 exhibit potential cytotoxicity in vitro against MCF-7, HepG-2 and DU-145 cell lines. The intrinsic binding constant (Kb) values of 1 (2.33 × 105 M-1) and 2 (2.46 × 105 M-1) evaluated from UV-Visible absorption studies suggest non-classical electrostatic mode of interaction via phosphate backbone of DNA double helix. The Stern- Volmer quenching constant (Ksv) of 1 (9.74 × 105 M-1) and 2 (2.9 × 106 M-1) determined by fluorescence studies suggests the groove binding and intercalation mode for 1 and 2, respectively. Effective cleavage of pBR322 DNA is induced by 1.Their interaction with DNA of cancer cells may account for potency.

Glucose-dependent Functional Heterogeneity In β-TC-6 Murine Insulinoma

To determine if the murine insulinoma, β-TC-6, is a suitable substitute for primary pancreatic β-cells in the study of β- cell functional heterogeneity, we used three distinct functional assays to ascertain the cell line-s response to glucose or a glucose analog. These assays include: (i) a 2-NBDG uptake assay; (ii) a calcium influx assay, and; (iii) a quinacrine secretion assay. We show that a population of β-TC-6 cells endocytoses the glucose analog, 2- NBDG, at different rates, has non-uniform intracellular calcium ion concentrations and releases quinacrine at different rates when challenged with glucose. We also measured the Km for β-TC-6 glucose uptake to be 46.9 mM and the Vm to be 8.36 x 10-5 mmole/million cells/min. These data suggest that β-TC-6 might be used as an alternative to primary pancreatic β-cells for the study of glucose-dependent β-cell functional heterogeneity.