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Figure 3: 5-Fluorouracil imparts its cytotoxic effect on quiescent KG1a cells in a dose-dependent manner: Serum-starved KG1a cells were incubated with
different concentrations of 5-FU (6 µg, 10 µg to 100 µg/mL) for 24 h and were subsequently subjected to MTT assay. As seen in the graph, QLCs displayed
a dose-dependent response to increasing concentrations of 5-FU. The data represent mean ± S.E.M. of three independent experiments (*** P ≤ 0.001)

Figure 4: Treatment with low concentrations of curcumin sensitizes the QLCs to the antimitotic agent, 5-FU: Serum-starved KG1a cells were incubated with
different concentrations of curcumin (10-100 µg/mL) for 48 h. After 48 h, the QLCs were further incubated with 5-FU (6 µg/mL) for another 24 h. When the
cells were subjected to MTT assay (E), it was observed that the percent proliferation of QLCs exposed to the combination treatment (10CU + 5-FU, 20CU
+ 5-FU) was lower than for the cells treated with only 5-FU. The data represent mean ± S.E.M. of three independed expriments (** P ≤ 0.01). (A-D) They
represent phase contrast images using a 20 × objective of an inverted microscope (Carl Zeiss, 200 × magnifications) of QLCs exposed to curcumin and/or
5-FU. (A) Vehicle control QLCs growing in clumps; (B) QLCs exposed to 10 µg/mL curcumin, showing maximum proliferation; (C) QLCs exposed to only 5-FU;
(D) QLCs exposed to 10 µg/mL curcumin and 5-FU, showing fewer cells, indicating that the QLCs have been more efficiently killed by 5-FU; (E) graphical
representation of QLCs subjected to MTT assay

to treatment, and their presence is associated with Quiescent leukemic cells prepared from KG1a
relapses. [13,15,16] In 2008, Vaidya et al. showed that get sensitized to low levels of 5-FU when treated
[36]
inhibition of p38 mitogen-associated protein kinase with low concentrations of curcumin
(MAPK) sensitizes the QLCs to antimitotic agents 5-FU Based on our previous studies, we wanted to examine
[36]
and cytosine arabinoside (Ara-C). Since the treatment of whether the proliferative response induced by low

QLCs with low concentrations of curcumin was pushing concentrations of curcumin treatment would make the
the cells into proliferation, we conjectured that this quiescent leukemic cells more susceptible to the mitotic
proliferative response could be translated to increase the inhibitor 5-FU. KG1a cells that were made quiescent
sensitivity of the leukemic cells to antimitotic agents. by serum deprivation were first treated with low
Hence, we first reconfirmed whether serum-starved KG1a concentrations of curcumin (10 µg/mL and 20 µg/mL)
cells were a good model system to study the effects of and then exposed to 6 µg/mL (lowest concentration) of
antimitotic drugs. We exposed the quiescent KG1a cells 5-FU. MTT assay was then carried out to assess the
[36]
to different concentrations of 5-FU and subjected them percent proliferation of the cells. It was observed [Figure
to MTT assay. As shown in Figure 3, 5-FU induced dose- 4E] that QLCs that were treated with a combination of
dependent killing of the quiescent KG1a cells, thereby 5-FU and low concentrations of curcumin were more
validating it as a good model system for testing the effectively killed (low percent proliferation: 60% and 65%
efficacy of antimitotic drugs. for 10 µg/mL and 20 µg/mL, respectively) as compared to
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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ July 8, 2016 ¦