The selective estrogen receptor modulator 4-hydroxy tamoxifen induces G1 arrest and apoptosis of multiple myeloma cell lines.
Multiple myeloma (MM) is an incurable hematological malignancy for which new therapeutic strategies should be envisaged. The selective estrogen receptor modulator (SERM), 4-hydroxy tamoxifen (4-OHTam), in the range of 1 to 10 micro M, was able to impair the cell proliferation of MM cell lines. This was achieved by blocking cells at the G1 phase of the cell cycle and by inducing apoptosis. This cellular response was observed in five out of six tested cell lines, all five expressing both alpha and beta estrogen receptor forms. No modifications of Bcl-2, Bcl-X, and Bax levels were observed, as well as no changes in Pi3K/Akt and JAK/STAT pathways that are often constitutively active in these cells. The signalization of 4-OHTam-induced cell death needs further investigation.
Gauduchon
Juliette
J
UPRES-EA 2128, UFR de Médecine, Université de Caen, Caen, France.
Gouilleux
Fabrice
F
Maillard
Sébastien
S
Marsaud
Véronique
V
Renoir
Michel J
MJ
Sola
Brigitte
B
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D009101:Multiple Myeloma; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene