Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 20 June 2023 / Approved: 21 June 2023 / Online: 21 June 2023 (08:45:41 CEST)

A peer-reviewed article of this Preprint also exists.

Rodríguez-Ruiz, M.; Ramos, M.C.; Campos, M.J.; Díaz-Sánchez, I.; Cautain, B.; Mackenzie, T.A.; Vicente, F.; Corpas, F.J.; Palma, J.M. Pepper Fruit Extracts Show Anti-Proliferative Activity against Tumor Cells Altering Their NADPH-Generating Dehydrogenase and Catalase Profiles. Antioxidants 2023, 12, 1461. Rodríguez-Ruiz, M.; Ramos, M.C.; Campos, M.J.; Díaz-Sánchez, I.; Cautain, B.; Mackenzie, T.A.; Vicente, F.; Corpas, F.J.; Palma, J.M. Pepper Fruit Extracts Show Anti-Proliferative Activity against Tumor Cells Altering Their NADPH-Generating Dehydrogenase and Catalase Profiles. Antioxidants 2023, 12, 1461.

Abstract

Cancer is considered nowadays one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds with anti-tumor attributes have been described, many of them from plant origin. 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 content (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 variety Alegría riojana, 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 pepper fruit crude extracts were determined including, among others, 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). Besides, 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 the 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.

Keywords

antioxidants; capsaicin; catalase; hepatoma; hydrogen peroxide; NADPH; nitric oxide; pancreas; hot pepper

Subject

Biology and Life Sciences, Agricultural Science and Agronomy

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