Design and Synthesis of Poly(2,2'-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations.

Chelation therapy is a medical procedure for removing toxic metals from human organs and tissues and for the treatment of diseases by using metal-chelating agents. For example, iron chelation therapy is designed not only for the treatment of metal poisoning but also for some diseases that are induced by iron overload, cancer chemotherapy, and related diseases. However, the use of such metal chelators needs to be generally carried out very carefully, because of the side effects possibly due to the non-specific complexation with intracellular metal cations. Herein, we report on the preparation and characterization of some new poly(bpy) ligands (bpy: 2,2'-bipyridyl) that contain one-three bpy ligand moieties and their anticancer activity against Jurkat, MOLT-4, U937, HeLa S3, and A549 cell lines. The results of MTT assays revealed that the tris(bpy) and bis(bpy) ligands exhibit potent activity for inducing the cell death in cancer cells. Mechanistic studies suggest that the main pathway responsible for the cell death by these poly(bpy) ligands is apoptotic cell death. It was also found that the anticancer activity of the poly(bpy) ligands could be controlled by the complexation (anticancer activity is turned OFF) and decomplexation (anticancer activity is turned ON) with biorelevant metal cations. In this paper, these results will be described.

A reversal in the vascularity of metastatic liver tumors from colorectal cancer after the cessation of chemotherapy plus bevacizumab: contrast-enhanced ultrasonography and histological examination.

OBJECTIVE: To assess the effect of chemotherapy plus bevacizumab on tumor vessels, as well as the reversibility of this effect, using contrast-enhanced ultrasonography (CEUS) and histology in patients with metastatic liver tumors derived from colorectal cancer. METHODS: The study included 12 patients who received chemotherapy plus bevacizumab, experienced a reduction in tumor vascularity as demonstrated by CEUS and consequently underwent liver resection. CEUS was performed before and after four courses of chemotherapy and before surgery. The numbers of microvessels highlighted by anti-CD34 antibodies in the viable tumor tissue were counted to quantify the microvessel density (MVD). As a control, 12 surgical specimens from 12 patients who had not received chemotherapy were examined. RESULTS: A reversal of tumor vascularity was observed in 10 of 12 patients. In two patients, the vascularity remained reduced. The MVD in the treatment group was significantly lower than that observed in the group without treatment. CONCLUSION: The data suggest that the tumor vessels regenerated substantially, although the effect of chemotherapy plus bevacizumab remained weak for approximately 6 weeks after the cessation of treatment. Therefore, future research must determine whether bevacizumab should be used prior to surgery.