Novel Gold and Silver Carbene Complexes Exert Antitumor Effects Triggering the Reactive Oxygen Species Dependent Intrinsic Apoptotic Pathway

Abstract

Cisplatin and other platinum-based drugs are well-known valid anticancer drugs. However, during chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance has pushed many research groups to devise new metal-based compounds holding improved anticancer properties and fewer undesired effects. Amongst the variety of synthesized compounds, significant antiproliferative effects have been obtained by employing organometallic compounds, particularly those based on silver and gold. With this in mind, we synthesized four compounds, two silver complexes and two gold complexes, with good inhibitory effects on the in vitro proliferation of breast and ovarian cancer-cell models. The antitumor activity of the most active compound, that is, AuL4, was found to be ninefold higher than that of cisplatin, and this compound induced dramatic morphological changes in HeLa cells. AuL4 induced PARP-1 cleavage, caspases 3/7 and 9 activation, mitochondria disruption, cytochrome c release in cancer-cell cytoplasm, and the intracellular production of reactive oxygen species. Thus, AuL4 treatment caused cancer-cell death by the intrinsic apoptotic pathway, whereas no cytotoxic effects were recorded upon treating non-tumor cell lines. The reported outcomes may be an important contribution to the expanding knowledge of medicinal bio-organometallic chemistry and enlarge the available anticancer toolbox, offering improved features, such as higher activity and/or selectivity, and opening the way to new discoveries and applications.

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

“…The mechanism of action is associated to ROS production [69] and the mitochondrial membrane potential loss, by increasing Bax expression and decreasing Bcl-2 expression. Bax and Bak oligomers form pores, which increase the permeability of the external mitochondrial membrane, releasing cytochrome c in the cytoplasm, which is an apoptosis characterizing event [70][71][72]. The release of cytochrome c from mitochondria to cytosol leads to the formation of apoptosomes, and consequently, the activation of caspase-9, which activates the cascade of the effector caspases [49,73,74].…”

Blue-emitting acridine-tagged silver(i)-bis-N-heterocyclic carbene

“…[1][2][3][4][5][6][7][8][9][10][11] Moreover, the silver-NHC complexes have been lately accredited as the building blocks of an effective antimicrobial agent to display phosphorescence emission. [12][13][14][15][16][17][18][19][20] Over the past few decades, numerous luminescent silver(I)-NHC complexes have been described. 21,22 Thus, it is clear that the N-substituents at the NHC counter ion and the coordination environment of the silver(I) center can signicantly contribute to the photophysical properties of the silver(I)-NHC complexes.…”

Newly Synthesized Imino-Derivatives Analogues of Resveratrol Exert Inhibitory Effects in Breast Tumor Cells

“…The effects of each compound on cell viability were determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, as previously reported [ 79 ]. Cells were seeded in quadruplicate in 96-well plates in regular growth medium and grown until 70–80% confluence.…”