Curcumin inhibits proliferation and induces apoptosis of leukemic cells expressing wild-type or T315I-BCR-ABL and prolongs survival of mice with acute lymphoblastic leukemia

Abstract

Objective: Curcumin, a natural compound derived from tumeric, has been shown to induce apoptosis in the leukemic cell line K562 and other cancer cell lines. However, it is unknown whether curcumin also has an inhibitory effect on BCR-ABL-expressing B-lymphoid cells. We tested whether curcumin has an inhibitory effect on BCR-ABL B-cell acute lymphoblastic leukemia (B-ALL) in vitro and in vivo.

Methods: Pre-B cells isolated from B6 mice expressing wild-type BCR-ABL (B6p210) and T315I mutant (B6T315I) were cultured in serial concentration of curcumin. Cultured cells were analyzed by automated cell counter, flow cytometry, western blotting, and transcription factor arrays. B-ALL was induced by transplantation of MSCV-GFP-p210 transduced donor marrow in lethally irradiated Balb/c mice. Diseased mice were treated with placebo or curcumin until death of the mice. Diseased mice were analyzed by flow cytometric and histopathological analyses.

Results: Curcumin inhibited the proliferation of B6p210 and B6T315I cells at concentration as low as 10 μM and induced apoptosis of the cells at concentrations of 30 μM. Using western blots and transcription factors arrays, we showed that curcumin decreased NF-κB levels and increased p53 levels. Curcumin decreased c-Abl levels in cells expressing the wild, but not the mutant, BCR-ABL oncogene. Curcumin treatment resulted in a statistically significant improved survival in diseased mice along with decreasing white blood and GFP cell counts.

Conclusions: Curcumin is effective against leukemic cells expressing p210 BCR-ABL and T315I BCR-ABL and holds promise in treating BCR-ABL-induced B-ALL.

Keywords:

• CURCUMIN
• LEUKEMIA
• BCR-ABL
• T315I
• NF-KB
• P53