Purpose: Cancer stem cells (CSCs) comprise a small population of cells within the total cancer cell population and are responsible for much of the self-renewal that occurs. The presence of CSCs represents a challenge in cancer treatment as they are often refractory to commonly used chemotherapeutic agents that kill the bulk of the cancer cells. While most cancer cells are destroyed by these agents, CSCs may remain and regenerate the tumor, necessitating the development of novel CSC-specific therapeutics. Curcumin, a bioactive compound derived from turmeric, has been found to eliminate CSCs in some cancers; however, it has not been adequately evaluated in lymphoma and leukemia CSCs. This study is to evaluate the effects of curcumin on Burkitt lymphoma and acute myeloid leukemia CSCs.
Methods: Three Burkitt lymphoma cells lines (BL41-3, DG-75, and Ramos) and an acute myeloid leukemia cell line (THP-1) were treated with varying concentrations of curcumin, followed by analysis of remaining cells for the presence of CSCs. CSC population was analyzed by ALDEFLOUR and colony formation assays. In addition, Western Blot analysis of various proteins involved in CSC self-renewal pathways (Wnt/β-catenin, SHH, and Notch pathways) was performed.
Results: Cell survival declined as the concentration of curcumin increased. Curcumin (1microM) decreased the ALDH-positive population of BL41-3 and DG-75 by ~50% and higher concentrations produced more significant reduction. A greater than 50% decrease in colony formation was observed in BL41-3, Ramos and DG-75 cells pre-treated with 5microM of curcumin, and pre-treatment with 10-20microM of curcumin reduced the colony by ~90% in BL41-3, Ramos and THP-1. Curcumin down-regulated Gli-1, Notch-1 and Cyclin D1.
Conclusion: Therefore, results from these experiments support the hypothesis that CSCs are decreased in lymphoma and leukemia cells treated with curcumin, potentially through the inhibition of self-renewal pathways, and provide a further rationale for developing curcumin as a novel therapeutic for these forms of cancer.
Aaron Domina– Associate Professor, Husson University, Bangor, Maine
Gi Lim– American University Of Antigua
Teralyn Chang– Husson Unversity, Maine
Tao Zhang– Assistant Professor, Husson University, Bangor, Maine