TY - JOUR
T1 - Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-κB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells
AU - Bhardwaj, Anjana
AU - Sethi, Gautam
AU - Vadhan-Raj, Saroj
AU - Bueso-Ramos, Carlos
AU - Takada, Yasunari
AU - Gaur, Upasna
AU - Nair, Asha S.
AU - Shishodia, Shishir
AU - Aggarwal, Bharat B.
PY - 2007/3/15
Y1 - 2007/3/15
N2 - Whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma (MM) cells by interfering with NF-κB and STAT3 pathways, was investigated. Resveratrol inhibited the proliferation of human multiple myeloma cell lines regardless of whether they were sensitive or resistant to the conventional chemotherapy agents. This stilbene also potentiated the apoptotic effects of bortezomib and thalidomide. Resveratrol induced apoptosis as indicated by accumulation of sub-G1 population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products, including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol downregulated the constitutive activation of AKT. These effects of resveratrol are mediated through suppression of constitutively active NF-κB through inhibition of IκBα kinase and the phosphorylation of IκBα and of p65. Resveratrol inhibited both the constitutive and the interleukin 6-induced activation of STAT3. When we examined CD138+ plasma cells from patients with MM, resveratrol inhibited constitutive activation of both NF-κB and STAT3, leading to down-regulation of cell proliferation and potentiation of apoptosis induced by bortezomib and thalidomide. These mechanistic findings suggest that resveratrol may have a potential in the treatment of multiple myeloma.
AB - Whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma (MM) cells by interfering with NF-κB and STAT3 pathways, was investigated. Resveratrol inhibited the proliferation of human multiple myeloma cell lines regardless of whether they were sensitive or resistant to the conventional chemotherapy agents. This stilbene also potentiated the apoptotic effects of bortezomib and thalidomide. Resveratrol induced apoptosis as indicated by accumulation of sub-G1 population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products, including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol downregulated the constitutive activation of AKT. These effects of resveratrol are mediated through suppression of constitutively active NF-κB through inhibition of IκBα kinase and the phosphorylation of IκBα and of p65. Resveratrol inhibited both the constitutive and the interleukin 6-induced activation of STAT3. When we examined CD138+ plasma cells from patients with MM, resveratrol inhibited constitutive activation of both NF-κB and STAT3, leading to down-regulation of cell proliferation and potentiation of apoptosis induced by bortezomib and thalidomide. These mechanistic findings suggest that resveratrol may have a potential in the treatment of multiple myeloma.
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U2 - 10.1182/blood-2006-02-003988
DO - 10.1182/blood-2006-02-003988
M3 - Article
C2 - 17164350
AN - SCOPUS:33947197883
SN - 0006-4971
VL - 109
SP - 2293
EP - 2302
JO - Blood
JF - Blood
IS - 6
ER -