Pepper Fruit Extracts Show Anti-Proliferative Activity against Tumor Cells Altering Their NADPH-Generating Dehydrogenase and Catalase Profiles

Abstract

Cancer is considered one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds from plant origin with anti-tumor attributes have been described. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory, and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work, the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin contents (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the Alegría riojana variety, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with crude pepper fruit extracts were determined including protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), among others. In addition, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced their catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H2O2 and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines.

Exogenous Application of Melatonin on the Preservation of Physicochemical and Enzymatic Qualities of Pepper Fruit from Chilling Injury

“…The prolonged exposure to low temperatures might activate the enzymatic AO system in pepper fruits to respond to physiological stress by increasing the activities of SOD, CAT, and POD [10]. Rodríguez-Ruiz et al [5] reported that CAT activity in pepper fruit is higher than that of SOD and POD due to the modulation of the CAT gene and its activities during the fruit ripening and senescence process. Among the tested samples, the MT-treated samples displayed slightly higher AO enzyme activity.…”

“…The primary cause of pepper fruit softening is its cell wall polysaccharides, and certain enzymes that hydrolyze the cell wall-like PG, PME, pectin lyases (PLs), β-galactosidases (β-Gals), endo-1, and 4-β-D-glucanases (EGases)-become extremely active and negatively alter the texture of the pepper fruits [4]. Furthermore, pepper fruit deterioration due to its weakened stress response system has also been widely reported, as shown by decreased activity of AO enzymes such as SOD, POD, and CAT, which are the robust antioxidant systems in plants that effectively slow down the senescence process [5]. Proper storage is crucial for preserving the freshness of green pepper fruits for extended periods.…”