Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

Abstract

Overexpression of cyclooxygenase-2 (COX-2) and prostaglandins (PG) is linked to a wide variety of human cancers. Here, we assessed whether the chemotherapeutic effect of grape seed proanthocyanidins (GSP) on non-small cell lung cancer (NSCLC) cells is mediated through the inhibition of COX-2 and PGE 2 /PGE 2 receptor expression. The effects of GSPs on human NSCLC cell lines in terms of proliferation, apoptosis, and expression of COX-2, PGE 2 , and PGE 2 receptors were determined using Western blotting, fluorescence-activated cell sorting analysis, and reverse transcription-PCR. In vitro treatment of NSCLC cells (A549, H1299, H460, H226, and H157) with GSPs resulted in significant growth inhibition and induction of apoptosis, which were associated with the inhibitory effects of GSPs on the overexpression of COX-2, PGE 2 , and PGE 2 receptors (EP1 and EP4) in these cells. Treatment of cells with indomethacin, a pan-COX inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell growth and induced cell death. The effects of a GSP-supplemented AIN76A control diet fed to nude mice bearing tumor xenografts on the expression of COX-2, PGE 2 , and PGE 2 receptors in the xenografts were also evaluated. The growth-inhibitory effect of dietary GSPs (0.5%, w/w) on the NSCLC xenograft tumors was associated with the inhibition of COX-2, PGE 2 , and PGE 2 receptors (EP1, EP3, and EP4) in tumors. This preclinical study provides evidence that the chemotherapeutic effect of GSPs on lung cancer cells in vitro and in vivo is mediated, at least in part, through the inhibition of COX-2 expression and subsequently the inhibition of PGE 2 and PGE 2 receptors.Mol Cancer Ther; 9(3); 569-80. ©2010 AACR.

Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo

“…Cell viability was determined using an MTT assay. 29 As shown in Figure 2C, treatment of NSCLC cells with honokiol for 48 h resulted in a significant reduction in cell viability in a dose-dependent manner (60 μM dose; 40-70%, p < 0.001). We did not find significant inhibition of cell proliferation of BEAS-2B cells (4-10% inhibition) after honokiol treatment at the concentrations of 10, 20, 40 and 60 μM for 48 h. Moreover, the inhibition of cell viability of BEAS-2B cells by honokiol was significantly lower (p < 0.001) than the effect of equivalent concentrations of honokiol on the NSCLC cells at the same time points.…”

“…Cells were treated with honokiol or valproic acid for desired period of time and cell lysates were prepared as detailed previously. 29,43 Proteins were resolved on 8-12% SDS-PAGE and transferred onto the nitrocellulose membrane. Western blot analysis was performed to detect the expression levels of proteins of interest as detailed previously.…”

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

“…Small randomized trials have found beneficial effects of GSE for diabetic retinopathy and for vascular fragility (2). Recently, preclinical studies have shown that GSE inhibited human non-small cell lung cancer (NSCLC) xenografts growth in mice, in part, through the inhibition and downregulation of cyclooxygenase-2 (COX-2) and prostaglandin (PG) E 2 eicosanoid pathways (3).…”

Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis

“…For this study, we used the peripheral airway-derived adenocarcinoma cell line A549, because adenocarcinoma is currently the most common form of lung cancer and COX-2 levels are significantly higher in adenocarcinomas than in squamous cell carcinomas (26). For a positive control we used the non-selective COX inhibitor indomethacin, which has been proven to inhibit COX-2 activity and expression in NSCLC cells (27,28).…”