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Cited by 395Multiple Myeloma Research and TreatmentsSirtuins and Resveratrol in MedicineCytokine Signaling Pathways and Interactions

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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

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Bhardwaj, Anjana, Sethi, Gautam, Vadhan-Raj,, Saroj, Bueso-Ramos, Carlos, Takada, Yasunari, Gaur, Upasna, Nair, Asha S., Shishodia, Shishir, Aggarwal, Bharat B.·2007·Blood
DOI 10.1182/blood-2006-02-003988
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Abstract

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 down-regulated 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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  • Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.

    “Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.58,69–73”

    From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [72]

    The Discussion (page unavailable) links STAT3 activation to tumor-cell transformation and proliferation and reports constitutively active STAT3 in multiple myeloma and head and neck cancers. It does not specify head and neck squamous cell carcinoma or report constitutive STAT3 signaling in colorectal carcinoma, glioblastoma multiforme, or non-small cell lung cancer. Melanoma appears in a reference title, but not in the Discussion’s list of cancers with constitutively active STAT3. (LLM, conf=0.86)

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Metadata

Authors
Bhardwaj, A., Sethi, G., Vadhan-Raj, Bueso-Ramos, C., Takada, Y., Gaur, U., Nair, A. S., Shishodia, S., & Aggarwal, B. B.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Department of Cytokine and Supportive Oncology, The University of Texas M.D. Anderson Cancer Center, Houston;
  • Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston;
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2006-12-12
Volume
109
Issue
6
Pages
2293-2302
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2006-02-003988
OpenAlex
W2070124969
Cited by
395
References
3
Citations by year
2026: 8 · 2025: 8 · 2024: 10 · 2023: 12 · 2022: 11 · 2021: 20 · 2020: 17 · 2019: 19 · 2018: 26 · 2017: 20 · 2016: 23 · 2015: 17 · 2014: 14 · 2013: 30 · 2012: 30
FWCI
11.62
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
Multiple Myeloma Research Foundation
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords
resveratrol, multiple myeloma, chemoresistance, STAT3, NF-κB, apoptosis, cell proliferation, bortezomib, thalidomide, Akt, IκBα kinase, anti-apoptotic proteins, survivin, Bcl-2 family proteins, interleukin-6, CD138+ plasma cells, caspase-3
MeSH terms
Bortezomib, Resveratrol, Boronic Acids, Cell Survival, Enzyme Activation, Humans, Multiple Myeloma, Pyrazines, Stilbenes, Thalidomide, Tumor Cells, Cultured, Down-Regulation, Interleukin-6, Gene Expression Regulation, Neoplastic, NF-kappa B, Apoptosis, Drug Resistance, Neoplasm, Cell Proliferation, STAT3 Transcription Factor, bcl-2-Associated X Protein, Proto-Oncogene Proteins c-akt, Caspase 3, Syndecan-1

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