The Anti-Proliferative and Anti-Invasive Effect of Leaf Extracts of Blueberry Plants Treated with Methyl Jasmonate on Human Gastric Cancer In Vitro Is Related to Their Antioxidant Properties

Abstract

Gastric cancer is the third main cause of cancerous tumors in humans in Chile. It is well-accepted that a diet rich in antioxidant plants could help in fighting cancer. Blueberry is a fruit crop with a high content of antioxidants. Methyl jasmonate (MeJA) is a phytohormone involved in plant defenses under stress conditions. The exogenous application of MeJA can improve the antioxidant properties in plants. We studied in vitro and in vivo anticancer action on human gastric cancer (cell line AGS) and the antioxidant properties of extracts from blueberry plants untreated and treated with MeJA. The results demonstrated that leaf extracts displayed a higher inhibition of cancer cell viability as well as greater antioxidant properties compared to fruit extracts. Besides, MeJA applications to plants improved the antioxidant properties of leaf extracts (mainly anthocyanins), increasing their inhibition levels on cell viability and migration. It is noteworthy that leaf extract from MeJA-treated plants significantly decreased cancer cell migration and expression of gastric cancer-related proteins, mainly related to the mitogen-activating protein kinase (MAPK) pathway. Interestingly, in all cases the anticancer and antioxidant properties of leaf extracts were strongly related. Despite highlighted outcomes, in vivo results did not indicate significant differences in Helicobacter pylori colonization nor inflammation levels in Mongolian gerbils unfed and fed with blueberry leaf extract. Our findings demonstrated that MeJA increased antioxidant compounds, mainly anthocyanins, and decreased the viability and migration capacity of AGS cells. In addition, leaf extracts from MeJA-treated plants were also able to decrease the expression of gastric cancer-related proteins. Our outcomes also revealed that the anthocyanin-rich fraction of blueberry leaf extracts showed higher in vitro antiproliferative and anti-invasive effects than the crude leaf extracts. However, it is still uncertain whether the leaf extracts rich in anthocyanins of blueberry plants are capable of exerting a chemopreventive or chemoprotective effect against gastric cancer on an in vivo model.

Anthocyanin-Rich Extracts of Calafate (Berberis microphylla G. Forst.) Fruits Decrease In Vitro Viability and Migration of Human Gastric and Gallbladder Cancer Cell Lines

“…These authors indicated that the greatest inhibitory activity was found in the anthocyanin fraction, with a 50% inhibition of cellular proliferation, concluding that the blueberry intake could reduce the colon cancer risk. Accordingly with our results, Ribera-Fonseca et al (2020) reported that anthocyaninrich extracts of highbush blueberry significantly decreased A G S c e l l v i a b i l i t y b y a r o u n d 2 0 -3 0 % a t 100 μg mL −1 compared to the negative and positive control (quercetin 4 μM). Peiffer (2018) pointed out that the preparation of fractions possessing enriched amounts of the active constituents of Black Raspberry, including anthocyanins, protocatechuic acid, quercetin, ellagic acid (all of which have exhibited anti-cancer properties), may improve patients' access to the anti-cancer benefits afforded by this species.…”

“…On this basis, it has been suggested that they could be potential therapeutic tools against the co-morbidity associated with the development of obesity. Lately, Ribera-Fonseca et al (2020) found that leaf extracts of highbush blueberry at a concentration equal or higher than 400 μg mL −1 caused more than 50% of AGS cell viability inhibition, reaching 60% of inhibition at the highest doses studied (3200 μg mL −1 ). In contrast, fruit extract provoked only about 10% of inhibition of AGS cell viability at extract exposure during 48 h at the highest concentrations (1600 μg mL −1 ).…”

“…Anthocyanin-rich extracts of Calafate fruits were obtained by chromatography fractionation of dried crude extracts using a glass column of 2.5 cm diameter (Fig. 1c), as described by Ribera-Fonseca et al (2020). Briefly, the cotton pad was placed at the end of the column, which was packed with silica gel previously dissolved in dichloromethane to reach 12 cm of height.…”

“…1e) using a plate reader PHOmo (AutobioLabtec Instruments Co. Ltd., Zhengzhou Henan, China). This procedure was carried out similarly to that performed by Ribera-Fonseca et al (2020). The percentage of cell viability was calculated using the formula: Cell viability (%) = (X × 100%)/Y, where "X" is the absorbance of treated cells and "Y" the absorbance of untreated cells.…”

“…Cell migration was measured in AGS and G415 cells, also in a similar manner to that performed by Ribera-Fonseca et al (2020). Assays were performed using 24-well plates containing polycarbonate filters with an 8-μm pore size (BD Biosciences, Bedford, MA, USA).…”