Mechanism of arctigenin-mediated specific cytotoxicity against human lung adenocarcinoma cell lines

The lignan arctigenin (ARG) from the herb Arctium lappa L possesses anti-cancer activity, however the mechanism of action of ARG has been found to vary among tissues and types of cancer cells. The current study aims to gain insight into the ARC mediated mechanism of action involved in inhibiting proliferation and inducing apoptosis in lung adenocarcinoma cells. This study also delineates the cancer cell specificity of ARG by comparison with its effects on various normal cell lines. ARC selectively arrested the proliferation of cancer cells at the G(0)/G(1) phase through the down-regulation of NPAT protein expression. This down-regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7, while apoptosis was induced through the modulation of the Akt-1-related signaling pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH content was another factor influencing the susceptibility of cancer cells to ARC. These findings suggest that specific cytotoxicity of ARC against lung cancer cells was explained by its selective modulation of the expression of NPAT, which is involved in histone biosynthesis. The cytotoxicity of ARC appeared to be dependent on the intracellular GSH level. (C) 2013 Elsevier GmbH. All rights reserved.