Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappaB (NF-kappaB) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.
OriginalsprogEngelsk
TidsskriftCancer Research
Vol/bind65
Udgave nummer21
Sider (fra-til)9943-52
Antal sider9
ISSN0008-5472
DOI
StatusUdgivet - 2005

Fingeraftryk

Osteoclasts
Osteoblasts
Growth
Up-Regulation
Cathepsin K
Osteopontin
Osteocalcin
Cytoplasmic and Nuclear Receptors
Plasma Cells
Mesenchymal Stromal Cells
Osteogenesis
Cell Survival
Membrane Proteins
Down-Regulation
Apoptosis
Cell Line
Messenger RNA
Pharmaceutical Preparations
Neoplasms

Citer dette

@article{f783e900e11d11db9628000ea68e967b,
title = "Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation",
abstract = "Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappaB (NF-kappaB) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.",
keywords = "Apoptosis, Calcitriol, Carrier Proteins, Cell Differentiation, Cell Growth Processes, Cell Line, Tumor, Drug Synergism, Gene Expression Regulation, Neoplastic, Humans, Macrophage Colony-Stimulating Factor, Membrane Glycoproteins, Multiple Myeloma, Osteoblasts, Osteocalcin, Osteoclasts, Osteopontin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Calcitriol, Sialoglycoproteins, Stilbenes",
author = "Patrice Boissy and Andersen, {Thomas L} and Abdallah, {Basem M} and Moustapha Kassem and Torben Plesner and Jean-Marie Delaiss{\'e}",
year = "2005",
doi = "10.1158/0008-5472.CAN-05-0651",
language = "English",
volume = "65",
pages = "9943--52",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research (A A C R)",
number = "21",

}

Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation. / Boissy, Patrice; Andersen, Thomas L; Abdallah, Basem M; Kassem, Moustapha; Plesner, Torben; Delaissé, Jean-Marie.

I: Cancer Research, Bind 65, Nr. 21, 2005, s. 9943-52.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation

AU - Boissy, Patrice

AU - Andersen, Thomas L

AU - Abdallah, Basem M

AU - Kassem, Moustapha

AU - Plesner, Torben

AU - Delaissé, Jean-Marie

PY - 2005

Y1 - 2005

N2 - Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappaB (NF-kappaB) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

AB - Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappaB (NF-kappaB) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

KW - Apoptosis

KW - Calcitriol

KW - Carrier Proteins

KW - Cell Differentiation

KW - Cell Growth Processes

KW - Cell Line, Tumor

KW - Drug Synergism

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Macrophage Colony-Stimulating Factor

KW - Membrane Glycoproteins

KW - Multiple Myeloma

KW - Osteoblasts

KW - Osteocalcin

KW - Osteoclasts

KW - Osteopontin

KW - RANK Ligand

KW - Receptor Activator of Nuclear Factor-kappa B

KW - Receptors, Calcitriol

KW - Sialoglycoproteins

KW - Stilbenes

U2 - 10.1158/0008-5472.CAN-05-0651

DO - 10.1158/0008-5472.CAN-05-0651

M3 - Journal article

C2 - 16267019

VL - 65

SP - 9943

EP - 9952

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -