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of several enzymes of the mitochondrial respiratory chain work by different mechanisms of action. In the present
including complex I, complex II-III, and complex IV in study, we have demonstrated that low concentrations of
the cells. [41,45,46] The inhibition of mitochondrial respiration curcumin push the quiescent leukemic cells into the cell
by NO may increase the electron leakage and cause the cycle, thereby sensitizing them to the antimitotic drug
formation of endogenous ROS (mainly superoxide anion), 5-fluorouracil. Although the molecular mechanism(s)
which can be observed in submitochondrial particles. [46-48] behind the inhibitory effect of the combination therapy
High levels of ROS may cause the oxidative damage on leukemic cells have yet to be explained, this approach
of various cellular components and finally result in cell could be exploited to selectively target leukemic stem
death. [45,46] ROS is capable of causing oxidative damage cells that are responsible for relapse associated with
to biomacromolecules, leading to lipid peroxidation, leukemia, and to develop novel anticancer therapies for
oxidation of amino acid residues (especially cysteine the treatment of leukemia. Simultaneously, this approach
residues), formation of protein-protein cross-links, and could also be combined with other strategies employed
DNA oxidative damage. [41,49] Since we had seen a high in the ex vivo expansion of normal hematopoietic stem/
expression of NO in cells treated with the combination progenitor cells.
of curcumin and 5-FU, we were interested in finding out
whether these cells would also generate high levels of Acknowledgments
ROS. The QLCs treated with a combination of curcumin The authors wish to thank Symbiosis Centre for Research
and 5-FU were subjected to DCFDA assay. It was observed and Innovation (SCRI) and Symbiosis School of Biomedical
[Figure 8] that combination treatment [curcumin (10 µg/mL Sciences (SSBS), Symbiosis International University
and 20 µg/mL) + 5-FU (6 µg/mL)] led to an increase in the (SIU), Lavale, Pune, India for supporting the research
level of ROS generation (10 µg/mL = 80%, 20 µg/mL = work. Authors express gratitude to Dr. Vaijayanti P. Kale,
60%), as compared to that generated by only 5-FU treated National Centre for Cell Science (NCCS), Savitribai Phule
cells (40%). Pune University Campus, Pune, India for providing the
KG1a cell line as a kind gift.
DISCUSSION
Financial support and sponsorship
AML is a hematological malignancy that results from Nil.
transformation of multipotent hematopoietic progenitors
and leads to accumulation of immature myeloid cells in Conflicts of interest
the bone marrow. Many studies have shown that curcumin There are no conflicts of interest.
demonstrates antiproliferative, antioxidative, cytotoxic,
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