Page 19 - Read Online

Topic: Cancer Stem Cells: Impact on Treatment

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

Anagha Gardane, Mariyah Poonawala, Anuradha Vaidya
Symbiosis School of Biomedical Sciences, Symbiosis International University, Lavale, Pune 412115, India.
Correspondence to: Dr. Anuradha Vaidya, Deputy Director, Symbiosis School of Biomedical Sciences, Symbiosis International University,
Symbiosis Knowledge Village, Gram: Lavale, Taluka: Mulshi, District: Pune 412115, India. E-mail: dydirector@ssbs.edu.in

Dr. Anuradha Vaidya is the Deputy Director of Symbiosis School of Biomedical Sciences (SSBS), Symbiosis International
University (SIU), Pune. Broadly, her area of research is microenvironment-mediated regulation of stem cell fate. Areas of
expertise include Stem Cell Biology, Niche Biology, Experimental Hematology, Cancer Biology and Signal Transduction.

A B S T R AC T
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.

Key words: Acute myeloid leukemia; KG1a cell line; curcumin; 5-fluorouracil; quiescent leukemic cells

INTRODUCTION According to cancer stem cell (CSC) theory, CSCs are
responsible not only for tumor initiation, development,
Acute myeloid leukemia (AML) is a heterogeneous and metastasis but also for therapeutic resistance. [3,5-7]
clonal disorder of hematopoietic progenitor cells that These cells were first identified by Bonnet and Dick in
[8]
is characterized by a blockage of differentiation and an AML. Following their findings many other groups have
accumulation of immature non-functional myeloid cells identified these cells in various solid tumors, such as brain,
in the blood. It is the most common malignant myeloid breast, pancreas, and prostate. [9-12] Standard chemotherapy
[1]
disorder among children and adults. The mainstream and radiotherapy target only the active tumor cells.
[2]
approach for AML treatment is chemotherapy, radiation, or Quiescent CSCs evade therapy and remain unharmed,
surgery. [1,3] However, the association between conventional a major concern for the development of insensitivity
therapy and severe toxicity followed by a tendency to towards therapy leading to relapse associated with
relapse or metastasize cannot be ignored. [3,4] In many cases leukemia. [3,5,7] Furthermore, the release of inflammatory
resistance to therapy develops, leaving AML patients with
no alternative but to undergo bone marrow transplantation This is an open access article distributed under the terms of the Creative
(BMT) for a disease-free survival. [2,4] Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Access this article online terms.
Quick Response Code: For reprints contact: service@oaepublish.com
Website:
http://www.jcmtjournal.com
How to cite this article: Gardane A, Poonawala M, Vaidya A.
Curcumin sensitizes quiescent leukemic cells to anti-mitotic drug
5-fluorouracil by inducing proliferative responses in them. J Cancer
DOI: Metasta Treat 2016;2:245-52.
10.20517/2394-4722.2016.11
Received: 24-02-2016; Accepted: 27-04-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 245