Antigenotoxic and anticancer activities of plant extracts using different eukaryotic cell models
Year: 2017
Type: dissertation
Abstract: In the last decades, the interest in medicinal plants has increased significantly owing to the antioxidant properties found in their natural extracts, which are responsible for many therapeutic effects. Therefore, there has been a great demand in discovering novel compounds, in order to develop new products (e.g. pharmaceuticals, cosmetics and dietary) characterized by high efficiency and low toxicity. Genotoxic stress might be induced by external and internal factors, causing serious damage since many cellular events, such as replication and transcription, depend on DNA integrity. The colonic epithelium is continuously exposed to a large diversity of dietary compounds, some of them potentially carcinogenic, that may affect DNA integrity (e.g. DNA oxidation and strand breaks) and alter cell genetic information, contributing to the development of colorectal cancer (CRC). Diets that are mainly based on polyphenols have been associated with CRC prevention. Medicinal plant extracts may also be rich in polyphenols and can be used to prevent DNA damage. In this work, eukaryotic cellular models were used to assess the antigenotoxic activity of medicinal plant extracts known for their strong antioxidant activity: Ginkgo biloba (GBE) and Dittrichia viscosa (DVE). The extracts demonstrated protective effect in co-incubation with the clastogenic agent camptothecin, in viability assays using the yeast Schizosaccharomyces pombe. This effect suggests an antigenotoxic role for the extracts, which may result from the stimulation of DNA repair through the homologous recombination pathway. Moreover, the antigenotoxic effect of GBE and its digested product (DGBE), obtained through in vitro simulation of the human digestion, was investigated in the human colorectal adenocarcinoma cell line HT-29 against oxidative stress, using the comet assay. The results suggested that pre-treatment with GBE or DGBE protected the DNA from deleterious effects induced by the oxidizing agent H2O2, probably due to stimulation of antioxidant defence mechanisms and DNA repair or through induction of mild stress in cells, which caused adaption to oxidative stress. The antigenotoxic effect of GBE and DGBE can be antioxidantmediated, which is in accordance with the results of the in vitro antioxidant assays of iron chelation and scavenging of the radicals 2,2-diphenyl-1-picrylhydrazyl and nitric oxide and studies of intracellular oxidation with the fluorochrome 2',7'-dichlorodihydrofluorescein diacetate by flow cytometry, in Sch. pombe. Thus, DVE and GBE demonstrated protective effect against clastogenic damage and GBE protected the DNA from oxidative effects, an effect retained after the digestion, suggesting that GBE could be used in the prevention of CRC.
Author: Daniela dos Santos Oliveira
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2618350790