Curcumin sensitizes quiescent leukemic cells to antimitotic drug 5-fluorouracil by inducing proliferative responses in them

Abstract

Long-term quiescence or dormancy is a fundamental feature of cancer stem cells (CSCs) that are genetically identical to the malignant clone but constitute the only cells with tumor propagation potential within the overall tumor population. These quiescent cells show significant resistance to radiation and antiproliferative chemotherapy due to distinctive properties that seem to be related to their stem cell-like character. Hence, successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also the CSCs. Using serum-starved KG1a cell line as an experimental model system of quiescent leukemic cells (QLCs), the present study demonstrates that QLCs exposed to low concentrations of curcumin show high proliferative potential. Furthermore, when subjected to a combination therapy consisting of low concentrations of curcumin and 5-fluorouracil (5-FU), the QLCs displayed a high kill with an increase in the levels of nitric oxide (NO) and reactive oxygen species. These results were further consolidated with the observation of high caspase-3 activity in cells subjected to the combination therapy. This may suggest that low concentrations of curcumin stimulate the QLCs to become mitotically active, thereby sensitizing them to killing by the antimitotic drug, 5-FU.

Keywords

Acute myeloid leukemia / KG1a cell line / curcumin / 5-fluorouracil / quiescent leukemic cells

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