Chemosensitization by emodin, a plant-derived anti-cancer agent: mechanism of action.

摘要

Emodin (l,3,8-trihydroxy-6-methylanthraquinone) is a naturally occurring anthraquinone derivative, found in the roots and bark of certain planes, including rhubarb. Emodin, an active ingredient in various Chinese herbs, has been used for the medical treatment of a number of diseases, such as constipation, bacterial infection, and inflammation since ancient times (reviewed in refs. 1 and 2). In the mid 70s and early 80s, emodin was found to have cytotoxic activity against leukemia. Studies accumulated over the past few decades have clearly demonstrated that emodin is an active anti-cancer agent. Emodin has been shown to inhibit cell proliferation and cell cycle progression, to induce apoptosis, and to inhibit angiogenesis and metastasis both in in vitro cultured cancer cells and in vivo tumor xenograft models (reviewed in refs. 1 and 2). Furthermore, emodin, when supplied in drinking water, inhibited the formation of skin papillomas induced by DMBA-TPA two- stage skin carcinogenesis agents. The anti-cancer activities of emodin appear to be mediated through its inhibition, as a kinase inhibitor, of protein kinases CK2, p'561ck, Her-2eu and Janus-activated kinase 2 QAK2) (1, 2 and references therein)." Emodin was also found to inhibit the signaling pathways of PI3K-Cdc42/Rac-1-PAK, MAPK, VEGFR2, NFkB, and p53, to produce reactive oxygen species (ROS), to modulate the levels of Bcl-2 family members, to downregulate androgen receptor, and to promote cytochrome c mediated activation of PKCS, BAX, and caspase-3 (reviewed in refs. 1 and 2)7'