Title: Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/β-Catenin Signaling.
Abstract: Metal-based chemoimmunotherapy has recently garnered significant att Show more
Title: Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/β-Catenin Signaling.
Abstract: Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/β-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in β-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy. Show less
The chemical structures of Ru (II) complexes are known to affect their cellular behavior and toxicity. In this study, three new luminescent Ru (II) complexes, [Ru(bpy)2(HIPMP)](ClO4Show more
The chemical structures of Ru (II) complexes are known to affect their cellular behavior and toxicity. In this study, three new luminescent Ru (II) complexes, [Ru(bpy)2(HIPMP)](ClO4)2 (Ru1, bpy = 2,2'-bipyridine, HIPMP = 2-(1H-imidazo-[4,5-f] [1,10] phenanthrolin-2-yl)-4-methylphenol), [Ru(phen)2(HIPMP)](ClO4)2 (Ru2, phen = 1,10-phenanthroline), [Ru(dmb)2(HIPMP)](ClO4)2 (Ru3, dmb = 4,4'-dimethyl-2,2'-bipyridine), were synthesized, and their anticancer activities were examined. All three complexes displayed anticancer activities against various cancer cells, with Ru2 exhibiting the highest cytotoxic activities. Ru2 was shown to accumulate specifically in the endoplasmic reticulum (ER) and induce ER stress-mediated apoptosis. In addition, Ru2 could generate reactive oxygen species (ROS) and trigger mitochondrial membrane potential depolarization. These results demonstrated that Ru2 induced apoptosis in HeLa cells through ER stress and ROS production. Show less
Four ruthenium(ii) asymmetric complexes, [Ru(bpy)2(PAIDH)](2+) (bpy = 2,2'-bipyridine, PAIDH = 2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione, ), [Ru(phen)2(PAIDH)](2+) (phen = 1,10-phenanthroline, ), Show more
Four ruthenium(ii) asymmetric complexes, [Ru(bpy)2(PAIDH)](2+) (bpy = 2,2'-bipyridine, PAIDH = 2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione, ), [Ru(phen)2(PAIDH)](2+) (phen = 1,10-phenanthroline, ), [Ru(dmp)2(PAIDH)](2+) (dmp = 4,7-dimethyl-1,10-phenanthroline, ) and [Ru(dip)2(PAIDH)](2+) (dip = 4,7-diphenyl-1,10-phenanthroline, ), have been synthesized and characterized. These complexes displayed potent anti-proliferation activity against various cancer cell lines and had high selectivity between tumor cells and normal cells. HeLa cells exhibited the highest sensitivity to complex , accounting for the greatest cellular uptake. Complex was shown to accumulate preferentially in the mitochondria of HeLa cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarisation, and Bcl-2 and caspase family members activation. These results demonstrated that complex induced cancer cell apoptosis by acting on mitochondrial pathways. Show less
Two ruthenium(II) complexes [Ru(bpy)(2)(bfipH)](2+) (1) and [Ru(phen)(2)(bfipH)](2+) (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectrosc Show more
Two ruthenium(II) complexes [Ru(bpy)(2)(bfipH)](2+) (1) and [Ru(phen)(2)(bfipH)](2+) (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that the two complexes bind to DNA in an intercalative mode. Complexes 1 and 2 can efficiently photocleave pBR322 DNA in vitro under irradiation, singlet oxygen ((1)O(2)) was proved to contribute to the DNA photocleavage process. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru(II) complexes acted as efficient dual inhibitors of topoisomerases I and II. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. The AO/EB staining assay indicated that Ru(II) complexes could induce the apoptosis of HeLa cells. Show less
Three Ru(II) polypyridyl complexes with potential high DNA-binding ability have been designed and synthesized by extending the conjugated plane of the intercalative ligand and introducing electroposit Show more
Three Ru(II) polypyridyl complexes with potential high DNA-binding ability have been designed and synthesized by extending the conjugated plane of the intercalative ligand and introducing electropositive pendants to the ancillary ligand. Spectral titration, DNA thermal denaturation, viscosity experiments, and quantum chemistry calculations were performed, and the complexes were found to intercalate into DNA base pairs with very high affinity even at high salt concentrations. Benefiting from their high DNA-binding ability, the complexes can effectively inhibit the DNA transcription activity by blocking the binding of T7 RNA polymerase to the template DNA. As efficient transcription inhibitors, the complexes demonstrated high in vitro antitumor activity against four selected tumor cell lines. Show less