Abstract
Aralia elata Seem. is a traditional folk Chinese medicinal plant and its leaves have been used to treat many diseases. We aimed to evaluate the anti-breast cancer activity and safety pharmacology of the ethanol extract of A. elata Seem. leaves (ELE). Cytotoxicity was evaluated on human tumor cell lines by MTT assay in vitro. A tumor bearing-nude mice model was used to assess antitumor activity in vivo. Cell apoptosis was determined by Hoechst 33258 staining, flow cytometry and TUNEL staining. The protein levels were determined by western-blotting and immunohistochemical staining. In safety evaluation, ICR mice and beagle dogs were orally administered ELE at different doses to determine its adverse effects on the central nervous system and cardiorespiratory system. ELE significantly inhibited tumor growth and induced cell apoptosis in MCF-7 cells in vitro and in vivo. The protein levels including caspase-3, caspase-9, bax, bcl-2, PARP, and cytochrome c were significantly changed. For the central nervous system, no treatment-related changes in behavior, motor activity or coordination were observed in mice. For the cardiorespiratory system, no significant differences in cardiorespiratory parameters including heart rate, PR interval, RR interval, P wave duration, QRS duration, QTcF interval, respiratory frequency, tidal volume, body temperature, and blood pressure were observed in beagle dogs between the ELE treatment and control group. In conclusion, ELE possessed anti-breast cancer activity by activating a mitochondrial-mediated apoptotic pathway with high biological safety in animals, which indicates it could be a potential therapeutic agent for treating human breast cancer in the future.
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