Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

• DOI: 10.3892/or.2021.7962
• Publication Date: 2021-02-02T08:40:36Z
• Authors: Hao Zhou; Yichong Ning; Guirong Zeng; Chang Zhou; Xiaofeng Ding
• Keywords: Male; 0303 health sciences; Curcumin; Apoptosis; HL-60 Cells; Articles; Cell Cycle Checkpoints; Mice, SCID; U937 Cells; Genistein; Catechin; 3. Good health; Leukemia, Myeloid, Acute; Mice; 03 medical and health sciences; Mice, Inbred NOD; Resveratrol; Cell Line, Tumor; Animals; Humans; Phosphorylation; Proto-Oncogene Proteins c-akt

Curcumin, a phytochemical from rhizomes of the plant Curcuma longa, has been reported to exert potential anticancer properties in various cancer types, including acute myeloid leukemia (AML). However, the underlying mechanism remains poorly understood. The present study demonstrated that curcumin had a stronger cytotoxic activity against AML cells compared with three other types of phytochemicals (epigallocatechin gallate, genistein and resveratrol). Protein phosphorylation profiling using an antibody array identified that curcumin treatment increased the phosphorylation levels of 14 proteins and decreased those of four proteins. A protein‑protein interaction network was constructed using the STRING database, in which AKT was identified as a hub protein with the highest connectivity (PRAS40, 4E‑BP1, P70S6K, RAF‑1 and p27). Western blotting results indicated that curcumin dose‑dependently suppressed the phosphorylation of AKT, PRAS40, 4E‑BP1, P70S6K, RAF‑1 and p27 in AML cell lines (ML‑2 and OCI‑AML5). It was also demonstrated that curcumin regulated the cell cycle‑ and apoptosis‑related proteins (cyclin D1, p21, Bcl2, cleaved‑caspase‑3 and cleaved‑PARP), leading to cell cycle arrest and apoptosis in both ML‑2 and OCI‑AML5 cells. These effects of curcumin were enhanced by the AKT inhibitor afuresertib but were suppressed by the AKT activator SC‑79, indicating that curcumin functions via AKT. In the AML xenograft mouse model, curcumin and afuresertib synergistically suppressed the engraftment, proliferation and survival of AML cells. Collectively, the present study demonstrated that curcumin exerted anti‑AML roles by inactivating AKT and these findings may aid in the treatment of AML.