20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a newly identified natural product from Panax notoginseng, exhibits activity against a variety of cancer cells. Herein, we report the effects of this compound on human A549, H358, and H838 lung cancer cells, and compare these effects with a control lung epithelial cell line, BEAS-2B. 25-OCH3-PPD decreased survival, inhibited proliferation, and induced apoptosis and G1 cell cycle arrest in the lung cancer cell lines. The P. notoginseng compound also decreased the levels of proteins associated with cell proliferation and cell survival. Moreover, 25-OCH3-PPD inhibited the growth of A549 lung cancer xenograft tumors. 25-OCH3-PPD demonstrated low toxicity to non-cancer cells, and no observable toxicity was seen when the compound was administered to animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent in vitro and in vivo, and further preclinical and clinical development of this agent for lung cancer is warranted. © 2008 Elsevier Ireland Ltd. All rights reserved.