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Curcumin in combination with bortezomib synergistically induced apoptosis in human multiple myeloma U266 cells

Cited 54 time in Web of Science Cited 60 time in Scopus
Authors
Park, Juwon; Ayyappan, Vasudevan; Bae, Eun-Kyung; Lee, Chansu; Kim, Byung-Su; Kim, Byoung Kook; Lee, Young-Yiul; Ahn, Kwang-Sung; Yoon, Sung-Soo
Issue Date
2009-04-23
Publisher
Elsevier
Citation
Mol Oncol. 2008 Dec;2(4):317-26.
Keywords
Antineoplastic Combined Chemotherapy Protocols/pharmacologyApoptosis/*drug effectsBoronic Acids/*pharmacologyCell Line, TumorCell Proliferation/drug effectsCoculture TechniquesCurcumin/*pharmacologyCytokines/antagonists & inhibitorsDrug SynergismHumansInflammation Mediators/antagonists & inhibitorsMultiple Myeloma/*drug therapyPyrazines/*pharmacologyStromal Cells/cytology
Abstract
Growth of multiple myeloma cells is controlled by various factors derived from host bone marrow microenvironments. Interaction between multiple myeloma cells and bone marrow stromal cells (BMSCs) plays an important role in the expression of adhesive molecules and secretion of growth factors involved in multiple myeloma (MM) cell growth, survival, and resistance to anticancer drugs. Recently, the possibility of developing novel anti-cancer therapeutic strategies targeting both MM cells and MM cell-BMSC interactions has been discussed. Here we present data showing that curcumin, a major constituent of turmeric compounds extracted from the rhizomes of the plant Curcuma longa, effectively reduced the growth of MM cells and BMSCs. Upon treatment with curcumin, IL-6/sIL-6R-induced STAT3 and Erk phosphorylation was dramatically reduced in the co-cultured cells. In addition, curcumin inhibited the production of pro-inflammatory cytokines and VEGF, factors that are associated with the progression of multiple myeloma, from both MM cells and BMSCs. In a combination treatment with curcumin and bortezomib, IL-6/sIL-6R-induced STAT3 and Erk phosphorylation was effectively inhibited. Moreover, this combination treatment synergistically inhibited the growth of MM cells co-cultured with BMSCs as compared to controls. Taken together, these results indicate that curcumin potentiates the therapeutic efficacy of bortezomib in MM suggesting this combination therapy to be of value in the clinical management of MM.
ISSN
1878-0261 (Electronic)
Language
English
URI
http://hdl.handle.net/10371/62180
DOI
https://doi.org/10.1016/j.molonc.2008.09.006
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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