Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-κB and STAT3 pathways in Hodgkin's lymphoma cells

Gerardo Mackenzie, Nina Queisser, Manuel L. Wolfson, Cesar G. Fraga, Ana M. Adamo, Patricia I. Oteiza

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Although treatment of Hodgkin's lymphoma (HL) with a multidrug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-κB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-κB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-κB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalInternational Journal of Cancer
Volume123
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Curcumin
  • H-RS cells
  • Hodgkin's lymphoma
  • NF-κB
  • STAT3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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