Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic activities. This substance can be found in citrus fruits, grapes, olive oil, and peas. Considering that there are few studies in the literature on the toxicity of GA, the present work aimed to investigate its cytotoxic, mutagenic, and antimutagenic activities on HTC cells. GA was diluted in culture medium at the final concentration of 0.08, 0.16, 0.8, 1.6, and 8 μg/mL. The cytotoxicity was determined by the MTT assay and Trypan Blue exclusion method, with methyl methanesulfonate and doxorubicin as positive controls, respectively. The cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic activity with benzo[a]pyrene as positive control. Negative control received culture medium only. GA (0.08–8 μg/mL) was not cytotoxic to HTC cells by the MTT assay nor the Trypan Blue exclusion method as no statistical difference was observed when compared to the control. Concentration of 0.08 and 0.8 μg/mL showed no mutagenic or clastogenic effects, as no significant micronuclei inductions were observed, different from 8 μg/mL, that was mutagenic. Furthermore, none of the concentrations presented an antiproliferative activity. The antimutagenic activity of GA (0.08 μg/mL) was observed at the simultaneous treatment, as it reduced the frequency of micronuclei by 76% (24 h) and 79% (48 h). Although pre- and post-treatments were not statistically different from the mutagen, they reduced the induced-damage by 11% and 21%, respectively. The present study indicated the absence of cytotoxicity and antiproliferative activities of GA, in addition to their antimutagenic/protective effects that may contribute to human health.

This study reports the characterization and antiproliferative activity of exopolysaccharides (EPS) produced by submerged cultures of the endophytes Diaporthe sp. JF766998 and Diaporthe sp. JF767007 isolated from the medicinal plant Piper hispidum Sw. Both strains secreted a crude EPS that, upon size exclusion chromatography, showed to contain a heteropolysaccharide (galactose, glucose and mannose) and a high-molecular weight glucan. Data from methylation analysis, FTIR and NMR spectroscopy (1H, COSY, TOCSY and HSQC-DEPT) indicated that the purified glucan consisted of a main chain of glucopyranosyl β-(1→3) linkages substituted at O-6 by glucosyl residues. According to MTT assay, some treatments of both β-glucans have antiproliferative activity against human breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG2-C3A) cells after 24 and 48h of treatment, exhibiting a degree of inhibition ratio that reached the highest values at 400μg/mL: 58.0% (24h) and 74.6% (48h) for MCF-7 cells, and 61.0% (24h) and 83.3% (48h) for HepG2-C3A cells. These results represent the first reports on the characterization and antiproliferative effect of β-glucans from Diaporthe species and also expand the knowledge about bioactive polysaccharides from endophytic sources.

The consumption of healthy and natural foods has increased over the last few years, primarily because these foods are rich in substances with biological properties of interest, such as exerting anticancer effects and decreasing oxidative stress in living tissues. These foods support adequate nutrition, maintain health, and improve quality of life. Vanillic acid (VA) is a phenolic compound used widely in the food industry as a flavoring, preservative, and food additive. VA can be found in various cereals, whole grains, fruits, herbs, green tea, juices, beers, and wines and possesses antioxidant, hepatoprotective, cardioprotective, and antiapoptotic activities. Studying the cytotoxicity as well as the mutagenic and antimutagenic effects of different concentrations of VA in Rattus norvegicus hepatoma cells (HTC) can identify new cellular activities of this substance. Concentrations up to 100 µM VA are not cytotoxic to HTC cells in a MTT [3-(4,5-dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide] assay after 96-h exposure; therefore, VA does not compromise mitochondrial activity. Similarly, concentrations up to 500 µM do not compromise plasma membrane integrity. VA at 10 and 50 µM showed no mutagenic/clastogenic effects, as no significant micronuclei induction was observed. VA 10 µM presented no antiproliferative activity and reduced the cytotoxicity induced by benzo[a]pyrene. The antimutagenic activity of 10 µM VA was observed by the simultaneous, pre-, and post-treatments, as the phenolic compound significantly reduced the frequency of micronuclei induced by the mutagen. These results indicate that VA exerts different responses in HTC cells. Low concentrations present no cytotoxic, mutagenic, or antiproliferative effects and protect cells from DNA damage.

Background: St. John’s wort (Hypericum perforatum L.) is an herbaceous plant that is native to Europe, West Asia and North Africa and that is recognized and used worldwide for the treatment of mild and moderate depression. It also has been shown to be therapeutic for the treatment of burns, bruises and swelling and can be used for its wound healing, antiviral, antimicrobial, antioxidant, analgesic, hepato-protective and anxiolytic properties. The aim of this study was to evaluate the potential cytotoxic, mutagenic and antimutagenic action of H. Perforatum. Methods: Meristematic cells were used as the test system for Allium cepa L., and bone marrow cells from Rattus norvegicus, ex vivo, were used to calculate the mitotic index and the percentage of chromosomal aberration. Statistical analysis was performed using the chi-square test. Results: This medicinal plant had no cytotoxic potential in the vegetal test system evaluated. In the animal test system, none of the acute treatments, including intraperitoneal gavage and subchronic gavage, were cytotoxic or mutagenic. Moreover, this plant presented antimutagenic activity against the clastogenic action of cyclophosphamide, as confirmed in pre-treatment (76% reduction in damage), simultaneous treatment (95%) and post-treatment (97%). Conclusions: Thus, the results of this study suggest that the administration of H. perforatum, especially by gavage similar to oral consumption used by humans, is safe and with beneficial antimutagenic potential.

Background: Breast cancer is associated with a high mortality rate around the world due to its aggressiveness and high resistance to conventional therapies. Sanguinarine (SAN) and Chelerythrine (CHE) are plant alkaloids extracted from Sanguinaria canadensis and Macleaya cordata, which have been studied for their bioactivities. Objective: To determine the anticancer activities of Sanguinarine (SAN) and Chelerythrine (CHE) plant alkaloids. Method: The MTT assay, the alkaline comet assay and cell cycle analyses by flow cytometry were performed. Results: It was observed that SAN was cytotoxic to human breast adenocarcinoma cells (MCF-7) at concentrations of 7.5 µM (24 and 48 hours), effectively reducing cell viability from the concentration of 10 µM for 24 hours and 7.5 µM for 48 hours, by the MTT test. CHE, in turn, was cytotoxic at concentrations of 10 and 20 µM (48 hours), but did not compromise the cellular viability. The comet assay indicated that SAN was genotoxic to the MCF-7 cells, with a significant increment of damage at 10 µM, while none of the tested concentrations of CHE showed a genotoxic effect. The flow cytometry analysis indicated that no cell cycle arrest was caused by both alkaloids, but SAN 10 µM induced a sub-G1 cell population. Conclusion: The results of cytotoxicity, genotoxicity and cell cycle monitoring that are presented in this paper have suggested that SAN has more of a chemotherapeutic activity, as well as having the potential for the development of new therapies for breast cancer, when compared to CHE.

The investigation of traditionally used medicinal plants is valuable both as a source of potential chemotherapeutic drugs and as a measure of safety for the continued use of these medicinal plants.Achillea millefoliumL. (AM) is an ancient remedial herb native to Europe that is used to treat wounds, gastrointestinal and hepatobiliary disorders, inflammation, headaches, and pain.Bauhinia forficataLink (BF), an Asiatic plant, is one of the most commonly used plants in folk medicine against diabetes. The aim of this study was to evaluate the cytotoxic and antimutagenic potential of aqueous extracts of AM and BF on bone marrow cells of Wistar rats treatedin vivo. These plant extracts possess considerable antioxidant activity due to the presence of flavonoids and phenolic compounds. These compounds were determinants to noncytotoxic and antimutagenic/protective action of these plants, that reduced statistically the percentage of chromosomal alterations induced by the chemotherapeutic agent cyclophosphamide in simultaneous (AM, 68%; BF, 91%), pre- (AM, 68%; BF, 71%), and post-treatment (AM, 67%; BF, 95%). Therefore, the results of this study indicate that extracts ofA. millefoliumandB. forficatahave antimutagenic potential and that their consumption can benefit the health of those using them as an alternative therapy.