STAT3 is an oncoprotein which participates in essential processes of cell survival, growth and proliferation in many types of tumors, as well as immune diseases[3]. Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in cancer cells[3]. In vivo investigation suggested that brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues[4]. Brevilin A increased ROS levels, decreased MMP and induced apoptosis of CT26 cell in a dose-dependent manner. Higher apoptotic rates were achieved in CT26 cells treated with 2 μg/ml brevilin A compared to 2 μg/ml adriamycin, with a statistical significance of both compounds compared to control, indicating that brevilin A exerts a greater capacity in cell apoptosis induction than adriamycin[4]. Brevilin A significantly down-regulated the phosphorylation of PI3K, AKT and mTOR, and promoted the expression of LC3-II, which was a key protein in cell autophagy, in addition to the expression of autophagy-related proteins Beclin1 and Atg5, which indicated that PI3K/AKT/mTOR signaling was involved in CT26 autophagy induced by brevilin A[4]. Tumor weights of mice treated with brevilin A and adriamycin for 14 days were significantly lower compared to the control group (p < .01, p < .05) while the weight of those treated with brevilin A were significantly lower than that of the adriamycin group (p < .01). Body weights in adriamycin group were clearly lower than brevilin A group (p < .01), indicating that brevilin A exhibites lower toxicity compared to adriamycin[4]. The growth inhibition of the tumors by brevilin A reached 74.89% on day 14 after the inoculation, but the inhibition of tumor growth by adriamycin was 53.18%. In contrast with the control, brevilin A significantly promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues[4].
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