Dehydroepiandrosterone can inhibit the proliferation of myeloma cells and the interleukin-6 production of bone marrow mononuclear cells from patients with myeloma.
The serum levels of an adrenal sex hormone, dehydroepiandrosterone sulfate (DHEA-S), are significantly more decreased in human myelomas compared with the reduction brought by physiologic decline with age. In order to clarify the effect of DHEA on myeloma cells, we investigated whether DHEA and DHEA-S could inhibit interleukin-6 (IL-6) production of bone marrow mononuclear cells and the proliferation of myeloma cells from patients with myeloma. DHEA-S and DHEA suppressed IL-6 production from a bone marrow stromal cell line, KM-102, as well as in bone marrow mononuclear cells from patients with myeloma. Furthermore, DHEA inhibited in vitro growth of the U-266 cell line and primary myeloma cells from the patients, as well as the in vivo growth of U-266 cells implanted i.p. in severe combined immunodeficiency-hIL6 transgenic mice. DHEA up-regulated the expression of peroxisome proliferator-activated receptor (PPAR), PPAR beta, but not PPARgamma or PPARalpha, and the expression of IkappaBalpha gene in myeloma cells and bone marrow stromal cells, which could explain the suppressive effect of DHEA on IL-6 production through the down-regulation of NF-kappaB activity. Therefore, these data revealed that DHEA-S, as well as DHEA, had a direct effect on myeloma and bone marrow stromal cells to inhibit their proliferation and IL-6 production, respectively.
Liu
Shangqin
S
Department of Bio-Signal Analysis, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Ishikawa
Hideaki
H
Li
Fu-Jun
FJ
Ma
Zi
Z
Otsuyama
Ken-ichiro
K
Asaoku
Hideki
H
Abroun
Saeid
S
Zheng
Xu
X
Tsuyama
Naohiro
N
Obata
Masanori
M
Kawano
Michio M
MM
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008223:Lymphoma / Q000097:blood; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics; D048068:PPAR-beta / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012737:Sex Factors; D008258:Waldenstrom Macroglobulinemia / Q000097:blood; D051636:X-Linked Inhibitor of Apoptosis Protein
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D048068:PPAR-beta; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate