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Britannin is a natural pseudoguaiacane sesquiterpene lactone, which is reported to possess a significant anticancer function. However, its anticancer effects in T-cell lymphoblastic lymphoma (T-LBL) have not been studied. We investigated the molecular mechanisms of britannin's effective anticancer activity in T-LBL cells. We detected the proliferation, apoptosis, glucose consumption, and lactate production in T-LBL cells treated with or without britannin. We applied a mouse xenograft for in vivo study. The results showed that the IC50 for britannin in SUP-T1 and MOLT4 cells were 5.661 and 6.043 μM, respectively. Britannin inhibited the growth of T-LBL cells in vitro and in vivo. Besides this, britannin enhanced LC3 puncta formation, as well as LC3II and beclin1 expression in SUP-T1 and MOLT4 cells, while decreased p62 expression, indicating that britannin promoted the autophagy of T-LBL cells in vitro. Moreover, britannin promoted apoptosis and reduced glycolysis of T-LBL cells, which was reversed by the typical autophagic inhibitor chloroquine. Britannin increased the phosphorylation of AMPK, while decreasing the phosphorylation of mTOR and S6K1 in T-LBL cells. Moreover, the induction of autophagy in T-LBL cells by britannin was restrained by Compound C, the inhibitor of AMPK. Taken together, britannin mediated apoptosis and glycolysis of T-LBL cells in an autophagy-dependent manner, which was achieved by regulating AMPK/mTOR/S6K1 signaling, demonstrating its therapeutic potential against T-LBL. |
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