Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines

Azhar R. Hussain, Maqbool Ahmed, Naif A. Al-Jomah, Asma S. Khan, Pulicat Manogaran, Mehar Sultana, Jehad Abubaker, Leonidas C. Platanias, Khawla S. Al-Kuraya, Shahab Uddin

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

We provide evidence that curcumin, a natural compound isolated from rhizomes of plant Curcuma longa, induces apoptosis in several Burkitt's lymphoma cell lines expressing Bax protein (AS283A, KK124, and Pa682PB), whereas it has no effects in cell lines with no Bax expression (BML895 and CA46). Our data show that curcumin treatment results in down-regulation of constitutive activation of nuclear factor-κB (NF-κB) via generation of reactive oxygen species where it causes conformational changes in Bax protein leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and poly(ADP)-ribose polymerase cleavage leading to caspase-dependent apoptosis. In addition, curcumin treatment of Burkitt's lymphoma cell lines also causes upregulation of DR5; however, this up-regulation does not result in apoptosis. Importantly, cotreatment with curcumin and TRAIL induces apoptosis in Bax-deficient cell lines. Taken together, our findings suggest that curcumin is able to induce apoptosis in Bax-positive cell lines, whereas combinations with TRAIL result in apoptosis in Bax-negative cell lines. These findings also raise the possibility that incorporation of curcumin in treatment regimens may provide a novel approach for the treatment of Burkitt's lymphomas and provide the molecular basis for such future translational efforts.

Original languageEnglish
Pages (from-to)3318-3329
Number of pages12
JournalMolecular Cancer Therapeutics
Volume7
Issue number10
DOIs
Publication statusPublished - 1 Oct 2008

Fingerprint Dive into the research topics of 'Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines'. Together they form a unique fingerprint.

  • Cite this

    Hussain, A. R., Ahmed, M., Al-Jomah, N. A., Khan, A. S., Manogaran, P., Sultana, M., Abubaker, J., Platanias, L. C., Al-Kuraya, K. S., & Uddin, S. (2008). Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines. Molecular Cancer Therapeutics, 7(10), 3318-3329. https://doi.org/10.1158/1535-7163.MCT-08-0541