Cytotoxicity of lapachol metabolites produced by probiotics.

UNLABELLED: Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9ß-hexahydroindeno[1,2-ß]pyran-9ß-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 µmol l(-1) ) than lapachol (IC50 = 72.3 µmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 µmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess the effects of bacterial metabolism on drug performance and toxicity.

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.(AU)