Pepper Fruit Extracts Show Anti-Proliferative Activity against Tumor Cells Altering Their NADPH-Generating Dehydrogenase and Catalase Profiles
Marta Rodríguez-Ruiz1, María C Ramos2, María J Campos1
1Group of Antioxidants, Free Radicals and Nitric Oxide in Biotechnology, Food and Agriculture, Department of Stress, Development and Signaling in Plants, Estación Experimental del Zaidín (Spanish National Research Council, CSIC), 18008 Granada, Spain.
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.
Insights
Pepper extracts, independent of capsaicin content, show anti-proliferative effects on cancer cells. These extracts alter tumor cell metabolism, reducing NADPH generation and potentially triggering cell death, suggesting other compounds possess anti-tumor properties.
Area of Science:
- Biochemistry
- Oncology
- Plant Science
Background:
- Cancer is a leading cause of death, linked to altered oxidative metabolism.
- Natural compounds from plants, including capsaicin from peppers (Capsicum annuum L.), exhibit anti-tumor properties.
- Capsaicin is known for antioxidant, anti-inflammatory, and anti-proliferative activities.
Purpose of the Study:
- To investigate the anti-proliferative activity of pepper fruits with varying capsaicin levels against multiple tumor cell lines.
- To identify compounds in pepper fruits responsible for anti-tumor effects, beyond capsaicin.
- To examine the impact of pepper extracts on the oxidative and redox metabolism of liver and pancreas tumor cells.
Main Methods:
- Tested pepper fruit extracts from diverse Capsicum annuum L. varieties (California, Piquillo, Padrón, Alegría riojana) against lung, melanoma, hepatoma, colon, breast, pancreas, and prostate tumor cell lines.
- Analyzed effects of green Alegría riojana pepper extracts (low capsaicin) on protein nitration, S-nitrosation, antioxidant capacity, antioxidant enzyme activity (SOD, catalase, GPX), and NADPH-generating enzyme activity (G6PDH, 6PGDH, NADP-ICDH) in Hep-G2 and MIA PaCa-2 cells.
- Determined capsaicin content in different pepper varieties.
Main Results:
- Pepper's anti-proliferative activity did not correlate with capsaicin content; lower capsaicin levels were associated with greater activity.
- Pepper extracts significantly altered tumor cell antioxidant capacity, increased catalase activity, and substantially reduced NADPH-generating enzyme activity.
- Reduced availability of hydrogen peroxide (H2O2) and NADPH in treated cells suggests a mechanism for inhibiting proliferation and inducing cell death.
Conclusions:
- Compounds other than capsaicin in pepper fruits possess significant anti-tumor potential.
- Pepper fruit extracts modulate key metabolic pathways in cancer cells, impacting redox balance.
- These findings highlight the therapeutic potential of pepper extracts in cancer treatment, warranting further investigation into specific active compounds.
