The chemotherapeutic value of Astragalus membranaceus: from its total saponins to individual isoflavonoids

In the past decade, we have investigated the contemporary anti-inflammatory and anti-carcinogenic potential of different components of the Chinese medicinal herb Astragalus membranaceus. We have first exhibited that crude aqueous extract of Astragalus could protect against experimental colitis through modulation of colonic cytokines and adhesion molecules. We then discovered that the total Astragalus saponins (AST) could cause significant growth inhibition in human colon cancer cells as well as tumor xenograft, which synergistically worked with the chemotherapeutic drug 5-FU while alleviating the druginduced toxicity (Carcinogenesis 28:1347-55, 2007). AST has demonstrated anti-cancer activities in a wide range of human cancer cell lines, suggesting its universal chemotherapeutic property (Int. J. Cancer 125:1082-1091, 2009). AST undergoes a large variety of action mechanisms, including promotion of apoptosis, induction of phase-specific cell cycle arrest leading to inhibition of cell proliferation, ER stressinduced modulation of GRP78 and calpain deactivation through mediation of calcium homeostasis, reduction of oxidative stress, downregulation of pro-angiogenic and pro-invasive that results in inhibition of cell migratory and cell invasive actions. The signaling pathways and transduction molecules being identified as AST targets include NSAID-activated gene (NAG-1), PI3K-AST-mTOR pathway, ERK and NF-κB signaling. The anticancer effectiveness of AST was shown in both primary solid tumor as well as liver metastasis as demonstrated in different animal models. Besides, differential anti-carcinogenic actions of the isoflavonoids formononetin and calycosin were also explored in colon cancer, with unique modes of action of the latter compound such as modulation of NADPH oxidase and the tumor microenvironment.