Dataset Information

Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide.

ABSTRACT: Melanoma is one of the most aggressive and lethal form of cancer. Photodynamic therapy (PDT) is a clinically approved technique for cancer treatment, including non-melanoma skin cancer. However, the most of conventional photosensitizers are of low efficacy against melanoma due to the possible dark toxicity at high drug concentrations, melanin pigmentation, and induction of anti-oxidant defense mechanisms. In the current research we propose non-toxic flavin mononucleotide (FMN), which is a water-soluble form of riboflavin (vitamin B2) as a promising agent for photodynamic therapy of melanoma. We demonstrated selective accumulation of FMN in melanoma cells in vivo and in vitro in comparison with keratinocytes and fibroblasts. Blue light irradiation with dose 5?J/cm² of melanoma cells pre-incubated with FMN led to cell death through apoptosis. Thus, the IC₅₀ values of human melanoma A375, Mel IL, and Mel Z cells were in a range of FMN concentration 10-30?µM that can be achieved in tumor tissue under systemic administration. The efficiency of reactive oxygen species (ROS) generation under FMN blue light irradiation was measured in single melanoma cells by a label-free technique using an electrochemical nanoprobe in a real-time control manner. Melanoma xenograft regression in mice was observed as a result of intravenous injection of FMN followed by blue-light irradiation of tumor site. The inhibition of tumor growth was 85-90% within 50 days after PDT treatment.

SUBMITTER: Akasov RA

PROVIDER: S-EPMC6609768 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide.

Akasov R A RA Sholina N V NV Khochenkov D A DA Alova A V AV Gorelkin P V PV Erofeev A S AS Generalova A N AN Khaydukov E V EV

Scientific reports 20190704 1

Melanoma is one of the most aggressive and lethal form of cancer. Photodynamic therapy (PDT) is a clinically approved technique for cancer treatment, including non-melanoma skin cancer. However, the most of conventional photosensitizers are of low efficacy against melanoma due to the possible dark toxicity at high drug concentrations, melanin pigmentation, and induction of anti-oxidant defense mechanisms. In the current research we propose non-toxic flavin mononucleotide (FMN), which is a water- ...[more]

PMID: 31273268

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Project description:Soil bacteria can detoxify Cr(VI) ions by reduction. Within the last 2 decades, numerous reports of chromate reductase enzymes have been published. These reports describe catalytic reduction of chromate ions by specific enzymes. These enzymes each have sequence similarity to known redox-active flavoproteins. We investigated the enzyme NfoR from Staphylococcus aureus, which was reported to be upregulated in chromate-rich soils and to have chromate reductase activity (H. Han, Z. Ling, T. Zhou, R. Xu, et al., Sci Rep 7:15481, 2017, https://doi.org/10.1038/s41598-017-15588-y). We show that NfoR has structural similarity to known flavin mononucleotide (FMN) reductases and reduces FMN as a substrate. NfoR binds FMN with a dissociation constant of 0.4 μM. The enzyme then binds NADPH with a dissociation constant of 140 μM and reduces the flavin at a rate of 1,350 s-1 Turnover of the enzyme is apparently limited by the rate of product release that occurs, with a net rate constant of 0.45 s-1 The rate of product release limits the rate of observed chromate reduction, so the net rate of chromate reduction by NfoR is orders of magnitude lower than when this process occurs in solution. We propose that NfoR is an FMN reductase and that the criterion required to define chromate reduction as enzymatic has not been met. That NfoR expression is increased in the presence of chromate suggests that the survival adaption was to increase the net rate of chromate reduction by facile, adventitious redox processes.IMPORTANCE Chromate is a toxic by-product of multiple industrial processes. Chromate reduction is an important biological activity that ameliorates Cr(VI) toxicity. Numerous researchers have identified chromate reductase activity by observing chromate reduction. However, all identified chromate reductase enzymes have flavin as a cofactor or use a flavin as a substrate. We show here that NfoR, an enzyme claimed to be a chromate reductase, is in fact an FMN reductase. In addition, we show that reduction of a flavin is a viable way to transfer electrons to chromate but that it is unlikely to be the native function of enzymes. We propose that upregulation of a redox-active flavoprotein is a viable means to detoxify chromate that relies on adventitious reduction that is not catalyzed.

Project description:The purpose of this study was to evaluate the effects of the antimicrobial photodynamic therapy (a-PDT) with blue light and curcumin on oral disinfection during the 2?h after treatment.a-PDT is a technique that can potentially affect the viability of bacterial cells, with selective action targeting only areas with photosensitizer accumulation.A randomized controlled trial was undertaken. Twenty-seven adults were randomly divided into three groups: (1) the PDT group, which was treated with the drug, curcumin, and blue light (n=9); (2) the light group, which was treated only with the blue light, and no drug (n=9) and; (3) the curcumin group, which was treated only with the drug, curcumin, and no light (n=9). The irradiation parameters were: blue light-emitting diode (LED) illumination (455±30?nm), 400?mW of average optical power, 5?min of application, illumination area of 0.6?cm(2), 600?mW/cm(2) of intensity, and 200?J/cm(2) of fluence. A curcumin concentration of 30?mg/L was used. The saliva samples were collected for bacterial counts at baseline and after the experimental phases (immediately after treatment, and 1 and 2?h after treatment). Serial dilutions were performed, and the resulting samples were cultured on blood agar plates in microaerophilic conditions. The number of colony-forming units (CFU) was determined.The PDT group showed a significant reduction of CFU immediately after treatment (post-treatment) with PDT (5.71±0.48, p=0.001), and 1?h (5.14±0.92, p=0.001) and 2?h (5.35±0.76, p=0.001) after treatment, compared with pretreatment (6.61±0.82). There were no significant changes for the light group. The curcumin group showed a significant increase of CFU 1?h after treatment (6.77±0.40, p=0.02) compared with pretreatment (5.57±0.91) falling to baseline values at 2?h after treatment (5.58±0.70).The PDT group showed significant difference in microbial reduction (p<0.05) compared with both the light and curcumin groups until 2?h post-treatment. The new blue LED device for PDT using curcumin may be used for reduction of salivary microorganisms, leading to overall disinfection of the mouth (e.g., mucosa, tongue, and saliva), but new protocols should be explored.

Dataset Information

Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide.

Publications

Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide.

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