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 limitedtoxicity 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, mRNAexpression levels of proteins and survival of lung cancer cells in Vitro. Materials and
Methods: The A549 cellline was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyreneplus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stressparameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessedand results were compared among study groups.
Results: TQ treatment up-regulated Bax and down-regulatedBcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQdown-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased theexpression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treatedcells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated theexpression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantlydecreased when compared with the control group (p=0.004).
Conclusions: Our results revealed up-regulationof the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affectingthe induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights forunderstanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.