Flavonols ameliorate Benzo[a]pyrene-induced lung toxicity

Evaluation of ameliorative potential of isolated flavonol fractions from Thuja occidentalis in lung cancer cells and in Benzo(a)pyrene induced lung toxicity in mice

Avinaba Mukherjee1, Sourav Sikdar1 and Anisur Rahman Khuda-Bukhsh1*International Journal of Traditional and Complementary Medicine

1Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India.

Review method: Single-blind; Peer reviewer comments: 2.

Relative anticancer potentials of six flavonol fractions (F1-F6) isolated from Thuja occidentalis extract were first evaluated against lung cancer cells A549 in vitro, and fraction- F4 showing the maximum protective ability, was then tested in mice intoxicated with Benzo(a)pyrene (BaP), a known carcinogen with major effect on lung, to learn if this could also have ameliorative action against lung toxicity and tissue damage in mice in vivo. Chemical nature of F1-F6 fractions was confirmed with specific flavonol confirmatory test and mass spectral analysis; all fractions were tested for their possible anticancer effects against A549 cells. Results suggested that fraction 4 (F4) had the strongest anticancer effect. When treated to BaP intoxicated mice, F4 induced recovery of damaged lung tissue, presumably through inhibition of ROS generation, and enhanced production of major antioxidant molecules, that in turn blocked PI3K-activated expressions of Akt. Decrease in Bcl2/Bax ratio, over-expression of p53 gene and activation of caspase 3 were observed in tissues of F4 treated mice, further confirming apoptotic cell death as its major target. The F4 fraction of Thuja occidentalis extract showed remarkable apoptotic potential against lung cancer cells and ameliorative ability against BaP induced lung toxicity.

Flavonols ameliorate Benzo[a]pyrene-induced lung toxicity

Keywords: Flavonol; benzo[a]pyrene toxicity; lung toxicity; PI3K/Akt pathway; reactive oxygen species (ROS), Thuja occidentalis.

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