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Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2009 Apr; Vol. 8 (4), pp. 959-70. - Publication Year :
- 2009
-
Abstract
- Curcumin (diferuloylmethane), a yellow pigment in turmeric, has been shown to inhibit the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor closely linked to chemoresistance in multiple myeloma cells. Whether curcumin can overcome chemoresistance and enhance the activity of thalidomide and bortezomib, used to treat patients with multiple myeloma, was investigated in vitro and in xenograft model in nude mice. Our results show that curcumin inhibited the proliferation of human multiple myeloma cells regardless of their sensitivity to dexamethasone, doxorubicin, or melphalan. Curcumin also potentiated the apoptotic effects of thalidomide and bortezomib by down-regulating the constitutive activation of NF-kappaB and Akt, and this correlated with the suppression of NF-kappaB-regulated gene products, including cyclin D1, Bcl-xL, Bcl-2, TRAF1, cIAP-1, XIAP, survivin, and vascular endothelial growth factor. Furthermore, in a nude mice model, we found that curcumin potentiated the antitumor effects of bortezomib (P<0.001, vehicle versus bortezomib+curcumin; P<0.001, bortezomib versus bortezomib+curcumin), and this correlated with suppression of Ki-67 (P<0.001 versus control), CD31 (P<0.001 versus vehicle), and vascular endothelial growth factor (P<0.001 versus vehicle) expression. Collectively, our results suggest that curcumin overcomes chemoresistance and sensitizes multiple myeloma cells to thalidomide and bortezomib by down-regulating NF-kappaB and NF-kappaB-regulated gene products.
- Subjects :
- Animals
Blotting, Western
Boronic Acids administration & dosage
Bortezomib
Cell Proliferation drug effects
Curcumin administration & dosage
Drug Synergism
Humans
Immunoenzyme Techniques
Male
Mice
Mice, Nude
Multiple Myeloma metabolism
Multiple Myeloma pathology
NF-kappa B metabolism
Proto-Oncogene Proteins c-akt metabolism
Pyrazines administration & dosage
Signal Transduction
Thalidomide administration & dosage
Vascular Endothelial Growth Factor A metabolism
Xenograft Model Antitumor Assays
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Apoptosis drug effects
Disease Models, Animal
Drug Resistance, Neoplasm drug effects
Multiple Myeloma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1535-7163
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 19372569
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-08-0905