Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Liu S,Ishikawa H,Li FJ,Ma Z,Otsuyama K,Asaoku H,Abroun S,Zheng X,Tsuyama N,Obata M,Kawano MMdoi
10.1158/0008-5472.CAN-04-3079subject
Has Abstractpub_date
2005-03-15 00:00:00pages
2269-76issue
6eissn
0008-5472issn
1538-7445pii
65/6/2269journal_volume
65pub_type
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