D. P. Bancroft

Bio: D. P. Bancroft is an academic researcher. The author has contributed to research in topics: Cis–trans isomerism. The author has an hindex of 1, co-authored 1 publications receiving 47 citations.

Recognition of cisplatin adducts by cellular proteins.

Abstract: Cisplatin is a widely used chemotherapeutic agent. It reacts with nucleophilic bases in DNA and forms 1,2-d(ApG), 1,2-d(GpG) and 1,3-d(GpTpG) intrastrand crosslinks, interstrand crosslinks and monofunctional adducts. The presence of these adducts in DNA is through to be responsible for the therapeutic efficacy of cisplatin. The exact signal transduction pathway that leads to cell cycle arrest and cell death following treatment with the drug is not known but cell death is believed to be mediated by the recognition of the adducts by cellular proteins. Here we describe the structural information available for cisplatin and related platinum adducts, the interactions of the adducts with cellular proteins and the implications of these interactions for cell survival.

Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action.

Abstract: The cytotoxicity of transplatinum complexes of structural formula trans-[PtCl2(L)(L')] [L = L' = pyridine or thiazole, or L = quinoline (R' = methyl; R" = methyl, phenyl, or CH2phenyl) and L' = R'R"SO] has been studied in murine L1210 and human tumor cell lines. The results confirm previous observations that use of a sterically hindered planar ligand greatly enhances cytotoxicity, in comparison to trans-[PtCl2(NH3)2], such that in some cases cytotoxicity equivalent to that of the clinically used agent cisplatin [cis-[PtCl2(NH3)2]] is obtained. Results from both the panel of human ovarian carcinoma cell lines and the National Cancer Institute screening panel confirm a different pattern of cytotoxicity, with respect to cisplatin. The new trans-platinum complexes are also non-cross-resistant with cisplatin in both murine and human (human ovarian carcinoma panel) tumor cell lines. Preliminary mechanistic studies using both cis- and trans-[PtCl2(pyridine)2] in L1210 cells have been carried out, to delineate the reasons for both the dramatically enhanced cytotoxicity and the lack of cross-resistance with the clinically used agents. Intracellular uptake is enhanced for pyridine relative to ammine (NH3) complexes. The pyridine complexes also inhibit DNA synthesis, implying a role for DNA binding in their mechanism of action. Binding of the pyridine complexes to calf thymus DNA is, however, significantly less than for the analogous ammine complexes. The presence of trans-pyridine ligands results in steric hindrance, which retards the rate of reaction of trans-[PtCl2(pyridine)2], relative to trans[PtCl2(NH3)2], with other important biomolecules such as glutathione. The results point to a potential new class of platinum antitumor complexes acting by a new mechanism and with activity complementary to agents such as cisplatin.

Nonclassical platinum antitumor agents: perspectives for design and development of new drugs complementary to cisplatin.

Abstract: (1993). Nonclassical Platinum Antitumor Agents: Perspectives for Design and Development of New Drugs Complementary to Cisplatin. Cancer Investigation: Vol. 11, No. 5, pp. 578-589.

Cisplatin induces loop structures and condensation of single DNA molecules

Abstract: Structural properties of single lambda DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from approximately 52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed. Based on experimental results from both single-molecule and AFM studies, we propose a model to explain this kind of DNA condensation by cisplatin: first, di-adducts induce local distortions of DNA. Next, micro-loops of approximately 20 nm appear through distant crosslinks. Then, large aggregates are formed through further crosslinks. Finally, DNA is condensed into a compact globule. Experiments with Pt(dach)Cl(2) indicate that oxaliplatin may modify the DNA structures in the same way as cisplatin. The observed loop structure formation of DNA may be an important feature of the effect of platinum anti-cancer drugs that are analogous to cisplatin in structure.