Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

Abstract

Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 ) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI 2 ) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI 2 and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI 2 and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre-versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI 2 (as measured by 6-keto PGF1a) and 15-HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSEinduced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer. Cancer Prev Res; 9(12); 925-32. Ó2016 AACR.

S-Enantiomer of 19-Hydroxyeicosatetraenoic Acid Preferentially Protects Against Angiotensin II-Induced Cardiac Hypertrophy

“…The other two pathways that are involved in the formation of midchain HETEs are LOX and COX-2 enzymes. 5-LOX, 12-LOX, and 15-LOX enzymes metabolize AA to produce 5-, 12-, and 15-HETE, respectively (Porro et al, 2014;Radmark et al, 2015;Mao et al, 2016). In addition, it has been reported that minor quantities of midchain HETEs are produced by COX-2 enzyme (Bai and Zhu, 2008).…”

Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity

“…GSE is mainly used as a health food supplement to improve cardiovascular health [ 3 ]. Preclinical studies have shown antineoplastic effects of GSE against a variety of cancers, including lung cancer [ 4 – 9 ]. We recently reported that modulations of oncogenic microRNA (miRNA) or oncomir miR-19a/b, contributed to the antineoplastic properties of GSE against non-small cell lung cancer (NSCLC) and bronchial premalignant cells [ 8 ].…”

Consumo Nutricional De Frutas Y Vegetales en Ica, Perú: Estudio Poblacional Piloto

“…En este estudio, solo el número de frutas estuvo según lo sugerido. A pesar de, toda la comunicación social que existe a nivel mundial para el consumo de frutas por su alto contenido de polifenoles que contribuyen como agente protector antioxidante, a reducir riesgos de cáncer (Fu et al, 2011;Li et al, 2016) y las verduras igualmente, ante su protección anticancerígena y de enfermedades crónicas (Zhang et al, 2015), al menos se observó en este estudio gran consumo de una de las frutas como es la uva (Vaid & Katiyar, 2015;Mao et al, 2016) y del tomate como vegetal (Trejo et al, 2013;Aizawa et al, 2016) quienes son reconocidos por su gustación, más que el valor nutricional.…”