The Effects on Angiogenesis of Relevant Inorganic Chemotherapeutics

Abstract

: Angiogenesis is a key process allowing the formation of blood vessels. It is crucial for all the tissue and organs, ensuring their function and growth. Angiogenesis is finely controlled by several mechanisms involving complex interactions between pro- or antiangiogenic factors and an imbalance in this control chain may result in pathological conditions. Metals as copper, zinc and iron cover an essential role in regulating angiogenesis, thus therapies having physiological metals as target have been proposed. Also, some complexes of heavier metal ions (e.g Pt, Au, Ru) are currently used as established or experimental anticancer agents targeting genomic or non-genomic targets. These molecules may affect the angiogenic mechanisms determining different effects that have been only poorly and non-systematically investigated so far. Accordingly, in this review article we aim to recapitulate the impact on the angiogenic process of some reference anticancer drugs, and how it is connected to the overall pharmacological effects. Also, we highlight how the activity of these drugs can be related to the role of biological essential metal ions. Overall, this may allow a deeper description and understanding of the antineoplastic activity of both approved or experimental metal complexes, providing important insights for the synthesis of new inorganic drugs able to overcome resistance and recurrence phenomena.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…6 Copper levels have been reported to be higher in a variety of human malignancies, [7][8][9] including prostate, breast, colon, lung, and brain cancers, where excess copper concentration appears to be a necessary co-factor for angiogenesis. [10][11][12][13] Copper chelators as effective proteasome inhibitors and apoptosis inducers have been reported to be of therapeutic utility in the treatment of numerous types of cancers. [14][15][16] Copper, an essential element for all living things, is involved in a variety of physiological activities such as cellular metabolism, mopping of free radicals, neurotransmitter synthesis, cell growth, and angiogenesis.…”

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

“…Indeed, we have previously considered antiangiogenic effects underlying the antimetastatic activity of NAMI-A [ 120 , 140 ]. Several endothelial cell functions as well as distinct pathways can be affected, including the nitric oxide synthase (NOS) pathway, which activates the vascular endothelial growth factor (VEGF) and its receptors that are believed to be key factors of angiogenesis [ 173 ]. On the other hand, RAPTA-T seems to act mainly as an anti-metastatic agent by inhibiting invasive phenotypes of cancer cells [ 174 ].…”

Shape-dependent biological activity of spherical and quasi-spherical silver nanoparticles in E. coli, A549 cells and mice

“…Firstly, it is the suppression of copper transport to growing tumors, because they need copper for cuproenzymes Environmental Science: Nano Paper and neovascularization. [47][48][49] Secondly, the treatment of inflammation and fibrosis. 47 Thirdly, the replacement of tetrathiomolybdate, a toxic copper chelator, with silver to increase the effectiveness of cisplatin.…”