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Curcumin Induces Apoptotic Cell Death via Inhibition of PI3-Kinase/AKT Pathway in B-Precursor Acute Lymphoblastic Leukemia

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submitted on 2024-03-11, 06:54 and posted on 2024-03-11, 06:55 authored by Shilpa Kuttikrishnan, Kodappully S. Siveen, Kirti S. Prabhu, Abdul Quaiyoom Khan, Eiman I. Ahmed, Sabah Akhtar, Tayyiba A. Ali, Maysaloun Merhi, Said Dermime, Martin Steinhoff, Shahab Uddin

Acute lymphoblastic leukemia (ALL) is a significant cancer of children resulting from the clonal proliferation of lymphoid precursors with arrested maturation. Although chemotherapeutic approaches have been achieving successful remission for the majority of cases of childhood ALL, development of resistance to chemotherapy has been observed. Thus, new therapeutic approaches are required to improve patient's prognosis. Therefore, we investigated the anticancer potential of curcumin in ALL. We tested a panel of B-precursor ALL (B-Pre-ALL) cell lines with various translocations after treatment with different doses of curcumin. Curcumin suppresses the viability in a concentration-dependent manner in 697, REH, SupB15, and RS4;11 cells (doses from 0 to 80 μM). Curcumin induces apoptosis in B-Pre-ALL cell lines via activation of caspase-8 and truncation of BID. Curcumin treatment increased the ratio of Bax/Bcl-2 and resulted in a leaky mitochondrial membrane that led to the discharge of cytochrome c from the mitochondria to the cytoplasm, the activation of caspase 3 and the cleavage of PARP. Curcumin treatment of B-Pre-ALL cell lines induced a dephosphorylation of the constitutive phosphorylated AKT/PKB and a down-regulation of the expression of cIAP1, and XIAP. Moreover, curcumin mediates its anticancer activity by the generation of reactive oxygen species. Finally, the suboptimal doses of curcumin potentiated the anticancer activity of cisplatin. Altogether, these results suggest an important therapeutic role of curcumin, acting as a growth suppressor of B-Pre-ALL by apoptosis via inactivation of AKT/PKB and down-regulation of IAPs and activation of intrinsic apoptotic pathway via generation of Reactive Oxygen Species (ROS). Our interesting findings raise the possibility of considering curcumin as a potential therapeutic agent for the treatment of B-Pre-ALL.

Other Information

Published in: Frontiers in Oncology
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3389/fonc.2019.00484

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Frontiers

Publication Year

  • 2019

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Interim Translational Research Institute - HMC
  • National Center for Cancer Care and Research - HMC
  • Weill Cornell Medicine - Qatar

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