Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model
Mol Cancer Ther. 2009;8(4):959-70
|Multiple myeloma is a late-stage B-cell malignancy characterized by the infiltration of malignant plasma cells in bone marrow and is associated with high monoclonal protein in the blood. Multiple myeloma can occur de novo or can evolve from benign monoclonal gammapathy of undetermined significance that involves low levels of bone marrow plasmacytosis and monoclonal protein. Each year approximately 1% of patients with monoclonal gammapathy of undetermined significance develop multiple myeloma.|
Currently, high-dose chemotherapy and stem cell transplantation are the standard treatments followed for multiple myeloma. Although several newer drugs have been approved recently, treatment for multiple myeloma yet remains as a challenge.
Resistance to chemotherapy in multiple myeloma is not yet clear but has been evidenced that NF-κB may play a major role in pathogenesis of multiple myeloma. Thus, compounds like Curcumin, known to inhibit the activation of NF-κB, are effective against chemoresistance in multiple myeloma cells.
To investigate whether Curcumin can overcome chemoresistance and enhance the activity of thalidomide and bortezomib, used to treat patients with multiple myeloma, in vitro and in xenograft model in nude mice.
In vivo Study:
Results and Discussion:
Overall, Curcumin potentiated effects of bortezomib and thalidomide, and overcame chemoresistance as well as sensitized multiple myeloma cells by down-regulating NF-κB and NF-κB-regulated gene products.