Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells
Authors: Saroj Vadhan-Raj
Upasna Gaur
Carlos Bueso-Ramos
Anjana Bhardwaj
Bharat B Aggarwal
Shishir Shishodia
Yasunari Takada
Asha S Nair
Gautam Sethi
Journal: Blood (2007)
Discipline: CLINICAL MEDICINE
Keywords: resveratrol; multiple myeloma; proliferation; NF-kappaB; STAT3
Affiliations: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston;, Department of Cytokine and Supportive Oncology, The University of Texas M.D. Anderson Cancer Center, Houston;, Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston

Abstract:  Whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma (MM) cells by interfering with NF-kappaB 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-G(1) 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 down-regulated the constitutive activation of AKT. These effects of resveratrol are mediated through suppression of constitutively active NF-kappaB through inhibition of IkappaBalpha kinase and the phosphorylation of IkappaBalpha 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-kappaB 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. 

Retracted: No

PubPeer comments:
 August 15, 2013. On pages 2295 and 2300 in the 15 March 2007 issue, there are errors in Figure 1 and Figure 7. In Figure 1F, the images labeled as control and thalidomide were erroneously duplicated images of overlapping fields of the same original image. The appropriate independent images from the control and thalidomide conditions are now shown in the corrected Figure 1. The images for control and resveratrol-treated cells in Figures 1E and 1F were from the same experiment; therefore, the same images are shown in both panels. The corrected Figure 1 is shown below. ![file] In Figure 7C, the photomicrograph from patient 2 was erroneously duplicated as the patient 5 Res-100 u03bcM panel. The correct panel from patient 5 Res-100 u03bcM is now shown in the revised Figure 7 below. ![file] ,