Anticancer Effects of Thymoquinone, Caffeic Acid Phenethyl Ester and Resveratrol on A549 Non-small Cell Lung Cancer Cells Exposed to Benzo(a)pyrene A 549 cell line;adenocarcinoma;benzo(a)pyrene;caffeic acid phenylester;resveratrol;thymoquinone; 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.

Mean platelet volume (MPV) is inversely correlated with inflammation in inflammatory bowel diseases, rheumatoid arthritis, and ankylosing spondylitis as shown in the previous studies. It has been reported that elevated values of MPV are associated with cardiovascular diseases and stable chronic obstructive pulmonary disease (COPD). However, MPV values in acute exacerbation of COPD have not been investigated so far. This retrospective study was conducted to investigate the relationships between MPV and acute phase reactants and functional parameters during COPD exacerbation. The study included 47 patients with COPD with mild to very severe airway obstruction and 40 age‑matched healthy subjects. C‑reactive protein levels and complete blood count were analyzed and compared in patients during the stable period and during exacerbation of COPD. MPV values were 9.3 ±1.4 and 8.6 ±1.0 fl during stable period and during acute exacerbation, respectively. Mean MPV values in the control group were 9.3 ±0.8 fl. MPV values were significantly lower in patients during acute exacerbation than in those during the stable period of COPD and in control subjects (both, P <0.001). The results suggest that assessment of MPV in COPD exacerbation may indicate systemic inflammation. Thus, MPV may be used as a negative acute‑phase reactant in COPD exacerbation.

Surfactant Protein D (SP-D) is an important marker in chronic obstructive pulmonary disease (COPD). Serum SP-D levels increase while lung production of SP-D decreases in COPD. SP-D is a specific biomarker for monitoring COPD, assessment of exacerbation frequency and arrangement of treatment modalities. In the present study, we aimed to investigate the correlation between serum and induced sputum SP-D levels with severity and acute exacerbations of COPD.