Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells

Kovalchuk, Anna; Aladedunye, Felix; Rodriguez-Juarez, Rocio; Li, Dongping; Thomas, James E.; Kovalchuk, Olga; Przybylski, Roman

doi:10.4161/cbt.25935

Cited by 10 publications

(9 citation statements)

References 38 publications

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“…Using different cell types can show different responses towards a specific compound or plant extract. Some authors indicate that polyphenols are toxic to certain types of cancer cells that proliferate rapidly but are nontoxic to others [ 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

Bioactive Polyphenols from Southern Chile Seaweed as Inhibitors of Enzymes for Starch Digestion

et al. 2020

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The increment of non-communicable chronic diseases is a constant concern worldwide, with type-2 diabetes mellitus being one of the most common illnesses. A mechanism to avoid diabetes-related hyperglycemia is to reduce food digestion/absorption by using anti-enzymatic (functional) ingredients. This research explored the potential of six common Chilean seaweeds to obtain anti-hyperglycemic polyphenol extracts, based on their capacity to inhibit key enzymes related with starch digestion. Ethanol/water hot pressurized liquid extraction (HPLE), which is an environmentally friendly method, was studied and compared to conventional extraction with acetone. Total polyphenols (TP), antioxidant activity, cytotoxicity and inhibition capacity on α-glucosidase and α-amylase were analyzed. Results showed that the Durvillaea antarctica (cochayuyo) acetone extract had the highest TP content (6.7 ± 0.7 mg gallic acid equivalents (GAE)/g dry seaweed), while its HPLE ethanol/water extract showed the highest antioxidant activity (680.1 ± 11.6 μmol E Trolox/g dry seaweed). No extract affected cell viability significantly. Only cochayuyo produced extracts having relevant anti-enzymatic capacity on both studied enzymes, showing a much stronger inhibition to α-glucosidase (even almost 100% at 1000 µg/mL) than to α-amylase. In conclusion, from the Chilean seaweeds considered in this study, cochayuyo is the most suitable for developing functional ingredients to moderate postprandial glycemic response (starchy foods), since it showed a clear enzymatic inhibition capacity and selectivity.

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Section: Resultsmentioning

confidence: 99%

Bioactive Polyphenols from Southern Chile Seaweed as Inhibitors of Enzymes for Starch Digestion

et al. 2020

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“…In turn, the HaCaT cell line is a spontaneously immortalized aneuploid human keratinocyte cell line, hence the proliferative potential of these cells is similar to the other tested cell lines [ 40 ]. For this reason, we suspect that the differences in the response of the tested cells to the tested vanicosides are rather due to the differences in the metabolism of these substances by cancer cells and normal cells [ 41 , 42 ]. These differences may also be the result of the varied uptake rate or availability of cellular targets.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effect of Vanicosides A and B from Reynoutria sachalinensis against Melanotic and Amelanotic Melanoma Cell Lines and in silico Evaluation for Inhibition of BRAFV600E and MEK1

Nawrot-Hadzik

Choromańska

Abel

et al. 2020

IJMS

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Vanicosides A and B are the esters of hydroxycinnamic acids with sucrose, occurring in a few plant species from the Polygonaceae family. So far, vanicosides A and B have not been evaluated for anticancer activity against human malignant melanoma. In this study, we tested these two natural products, isolated from Reynoutria sachalinensis rhizomes, against two human melanoma cell lines (amelanotic C32 cell line and melanotic A375 cell line, both bearing endogenous BRAFV600E mutation) and two normal human cell lines—keratinocytes (HaCaT) and the primary fibroblast line. Additionally, a molecular docking of vanicoside A and vanicoside B with selected targets involved in melanoma progression was performed. Cell viability was studied using an MTT assay. A RealTime-Glo™ Annexin V Apoptosis and Necrosis assay was used for monitoring programmed cell death (PCD). Vanicoside A demonstrated strong cytotoxicity against the amelanotic C32 cell line (viability of the C32 cell line was decreased to 55% after 72 h incubation with 5.0 µM of vanicoside A), significantly stronger than vanicoside B. This stronger cytotoxic activity can be attributed to an additional acetyl group in vanicoside A. No significant differences in the cytotoxicity of vanicosides were observed against the less sensitive A375 cell line. Moreover, vanicosides caused the death of melanoma cells at concentrations from 2.5 to 50 µM, without harming the primary fibroblast line. The keratinocyte cell line (HaCaT) was more sensitive to vanicosides than fibroblasts, showing a clear decrease in viability after incubation with 25 µM of vanicoside A as well as a significant phosphatidylserine (PS) exposure, but without a measurable cell death-associated fluorescence. Vanicosides induced an apoptotic death pathway in melanoma cell lines, but because of the initial loss of cell membrane integrity, an additional cell death mechanism might be involved like permeability transition pore (PTP)-mediated necrosis that needs to be explored in the future. Molecular docking indicated that both compounds bind to the active site of the BRAFV600E kinase and MEK-1 kinase; further experiments on their specific inhibitory activity of these targets should be considered.

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“…The in vitro tissue models have also been used as an initial toxicity screen for novel materials that will be introduced into the oral cavity. Kovalchuk et al 2013 studied new lipid antioxidants which were designed to kill breast cancer cells. They utilized the EpiOral and EpiGingival tissue models and did not see any effects on tissue morphology or gene expression when tissues were exposed to the lipid antioxidants (Kovalchuk et al 2013).…”

Section: Oral Irritation and Cytotoxicitymentioning

confidence: 99%

In vitro three-dimensional organotypic culture models of the oral mucosa

Klausner

Handa²,

Aizawa

2021

In Vitro Cell.Dev.Biol.-Animal

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Three-dimensional, organotypic models of the oral mucosa have been developed to study a wide variety of phenomena occurring in the oral cavity. Although a number of models have been developed in academic research labs, only a few models have been commercialized. Models from academic groups offer a broader range of phenotypes while the commercial models are more focused on the oral and gingival mucosa. The commercialized models are manufactured under highly controlled conditions and meet the requirements of quality standards, which leads to high levels of reproducibility. These in vitro models have been used to evaluate the irritancy of oral care products such as toothpastes, mouthwashes, and mucoadhesives. The effects of cigarette smoke on oral cavity tissues have been studied and compared to those of e-cigarettes. Oral tissue models have facilitated investigation of the mechanisms of oral mucositis and oral candidiasis and have been used to examine transbuccal drug delivery rates and the absorption of nanoparticles. Infection studies have investigated the effects of HIV-1 along with the effects of commensal and pathogenic bacteria. More recently, a differentiated oral tissue model has been shown to express the ACE2 receptor, which is known to be important for the receptor-mediated entry of the SARS-CoV-2 coronavirus into human cells and tissues. Hence, oral mucosal models may find application in determining whether viral infection of the oral mucosa is possible and whether such infection has implications vis-a-vis the current COVID-19 pandemic. As is apparent, these models are used in a broad variety of applications and often offer advantages versus animal models in terms of reproducibility, avoiding species extrapolation, and the ethical concerns related to human and animal experimentation. The goals of this paper are to review commercially available models of the human buccal and gingival mucosa and highlight their use to gain a better understanding of a broad range of phenomena affecting tissues in the oral cavity.

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Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells

Cited by 10 publications

References 38 publications

Bioactive Polyphenols from Southern Chile Seaweed as Inhibitors of Enzymes for Starch Digestion

Bioactive Polyphenols from Southern Chile Seaweed as Inhibitors of Enzymes for Starch Digestion

Cytotoxic Effect of Vanicosides A and B from Reynoutria sachalinensis against Melanotic and Amelanotic Melanoma Cell Lines and in silico Evaluation for Inhibition of BRAFV600E and MEK1

In vitro three-dimensional organotypic culture models of the oral mucosa

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