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The autophagy induced by curcumin via MEK/ERK pathway plays an early anti-leukemia role in human Philadelphia chromosome-positive acute lymphoblastic leukemia SUP-B15 cells


1 Department of Hematology and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, China
2 Department of Hematology, Sichuan Provincial People's Hospital, Chengdu 610041, Sichuan Province, China

Correspondence Address:
Ping Yu Gong,
Department of Hematology and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province
China
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Source of Support: None, Conflict of Interest: None

Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph + ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph + ALL. Materials and Methods: Ph + ALL cell line SUP-B15 was treated with curcumin. Cytotoxic activity of curcumin was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Signaling protein and specific maker of autophagy and conversion of LC3-I to LC3-II were determined by Western blot analysis. Cell apoptosis was determined by flow cytometry. Results: Curcumin treatment up-regulated the activation of RAF/MEK/ERK at 4 h and 8 h after curcumin exposure in SUP-B15 cells, curcumin treatment induced autophagy at exactly 4 h and 8 h after curcumin exposure. Curcumin exerted cytotoxic activity against SUP-B15 cells at 4 h and 8 h, which was independent of apoptosis. MEK specific inhibitor U0126 inhibited the occurrence of autophagy, and then blocked curcumin-induced cytotoxicity at 4 h and 8 h. Conclusions: Curcumin induce autophagic cell death in SUP-B15 cells via activating RAF/MEK/ERK pathway. These findings suggest that autophagic mechanism contribute to the curcumin-induced early SUP-B15 cell death, and autophagy is another anti-leukemia mechanism of curcumin.


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