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Enhanced Production and Anticancer Properties of Photoactivated Perylenequinones.

ABSTRACT: Hypocrellins and hypomycins are naturally occurring fungal perylenequinones with potential photodynamic activity against cancer and microbial diseases. This project pursued three lines of research. First, the production of perylenequinones was enhanced by investigating the effect of culture medium and light exposure on their biosynthesis. Solid-fermentation cultures on rice medium allowed for enhanced production of hypocrellins as compared to Cheerios or oatmeal medium. Alternatively, increased production of hypomycins, which are structurally related to the hypocrellins, was observed on oatmeal medium. In both cases, light exposure was an essential factor for the enhanced biosynthesis. In addition, this led to the discovery of two new perylenequinones, ent-shiraiachrome A (5) and hypomycin E (8), which were elucidated based on spectroscopic data. Finally, the photocytotoxic effects of both classes of compounds were evaluated against human skin melanoma, with EC₅₀ values at nanomolar levels for hypocrellins and micromolar levels for hypomycins. In contrast, both classes of compounds showed reduced dark toxicity (EC₅₀ values >100 μM), demonstrating promising phototherapeutic indices.

SUBMITTER: Al Subeh ZY

PROVIDER: S-EPMC7493285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light.

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Project description:Aggregation-induced emission (AIE) has, since its discovery, become a valuable tool in the field of nanoscience. AIEgenic molecules, which display highly stable fluorescence in an assembled state, have applications in various biomedical fields-including photodynamic therapy. Engineering structure-inherent, AIEgenic nanomaterials with motile properties is, however, still an unexplored frontier in the evolution of this potent technology. Here, we present phototactic/phototherapeutic nanomotors where biodegradable block copolymers decorated with AIE motifs can transduce radiant energy into motion and enhance thermophoretic motility driven by an asymmetric Au nanoshell. The hybrid nanomotors can harness two photon near-infrared radiation, triggering autonomous propulsion and simultaneous phototherapeutic generation of reactive oxygen species. The potential of these nanomotors to be applied in photodynamic therapy is demonstrated in vitro, where near-infrared light directed motion and reactive oxygen species induction synergistically enhance efficacy with a high level of spatial control.

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Anticancer properties of distinct antimalaria drug classes

2013-10-26 | GSE51739 | GEO

Photoactivated in Vitro Anticancer Activity of Rhenium(I) Tricarbonyl Complexes Bearing Water-Soluble Phosphines.

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Transcriptome analysis on fructose as the sole carbon source enhancing perylenequinones production of endophytic fungus <i>Shiraia</i> sp. Slf14.

Project description:Perylenequinones (PQ), a class of naturally occurring polypeptides, are widely used as a clinical drug for treating skin diseases and as a photodynamic therapy against cancers and viruses. In this study, the effects of different carbon sources on PQ biosynthesis by Shiraia sp. Slf14 were compared, and the underlying molecular mechanism of fructose as the sole carbon to enhance PQ production was investigated by transcriptome analysis. The results indicated that fructose enhanced PQ yield to 1753.64 mg/L, which was 1.73-fold higher than that obtained with glucose. Comparative transcriptome analysis demonstrated that most of the upregulated genes were related to transport systems, energy and central carbon metabolism in Shiraia sp. Slf14 cultured in fructose. The genes involved in glycolysis and pentose phosphate pathways, and encoding citrate synthase, ATP-citrate lyase, and acetyl-CoA carboxylase were substantially upregulated, resulting in increased overall acetyl-CoA and malonyl-CoA production. However, genes involved in gluconeogenesis, glyoxylate cycle pathway, and fatty acid synthesis were significantly downregulated, resulting in higher acetyl-CoA influx for PQ formation. In particular, the putative PQ biosynthetic cluster was upregulated in Shiraia sp. Slf14 cultured in fructose, leading to a significant increase in PQ production. The results of real-time qRT-PCR and related enzyme activities were also consistent with those of transcriptome analysis. These findings provide a remarkable insight into the underlying mechanism of PQ biosynthesis and pave the way for improvements in PQ production by Shiraia sp. Slf14.

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Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 1

Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response

2007-02-07 | GSE6960 | GEO

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