Comparison of the Anti-inflammatory Effects of Proanthocyanidin, Quercetin, and Damnacanthal on Benzo(a)pyrene Exposed A549 Alveolar Cell Line.

Phytochemical compounds are emerging as a new group of anti-inflammatory, antioxidant, and anti-cancer agents that help minimize toxicity in patients with pulmonary diseases. The goal of this study was to investigate the potential curative effects of Quercetin (QC), Damnacanthal (DAM), and Proanthocyanidine (PA) on inflammatory mediators and oxidative stress parameters and to examine the viability of the A549 cell line treated with benzo(a)pyrene (BaP) in vitro. The A549 cell line was treated with BaP, a BaP/QC combination, a BaP/DAM combination, and BaP/PA combination. Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and antiapoptotic proteins, and cell viability were assessed, and the results were compared. There were higher levels of lactate dehydrogenase after BaP treatment of A549 cell lines. Interferon-γ level significantly decreased in the QC, DAM, and PA-treated group (P < 0.001). IL-1ß and TNF-α levels significantly decreased after PA and QC treatments (P < 0.001). Some of the oxidative stress markers (NO, MDA, TOS) and OSI decreased, while antioxidant (GSH) levels increased after treatment with QC, DAM, and PA. The QC and DAM treatments profoundly upregulated apoptotic gene expression and downregulated antiapoptotic gene expression. Viability of QC, DAM, and PA-treated cells was found to be significantly higher in comparison to the control and BaP-treated groups (p < 0.001). Our results revealed that A549 cell lines treated with BaP-stimulated necrosis produced higher level of inflammatory cytokines and oxidative stress parameters. Treatments with PA, QC, and DAM reduced inflammatory response induced by BaP exposure.

Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene.

BACKGROUND: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. MATERIALS AND METHODS: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. RESULTS: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). CONCLUSIONS: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.