TY - JOUR
T1 - Multifactorial activities of nonsteroidal antiestrogens against leukemia
AU - Hayon, Tamar
AU - Atlas, Lena
AU - Levy, Etti
AU - Dvilansky, Alexander
AU - Shpilberg, Ofer
AU - Nathan, Ilana
N1 - Funding Information:
This study was supported by a grant from the Ministry of Health, Israel.
PY - 2003
Y1 - 2003
N2 - The antileukemic activity of nonsteroidal antiestrogens was investigated. Tamoxifen, clomiphene and nafoxidine caused a decrease in viability of the estrogen receptor-negative T-lymphoblastic leukemia cell line CCRF/CEM, nafoxidine being the most active. A combination of clomiphene and genistein resulted in a synergistic cytotoxic effect when applied to Molt-3, another T-lymphblastic leukemic cell line. The antiestrogens arrested the cells at G0/G1 phase and induced apoptosis. Using the CCRF/VCR 1000 cell line, which is resistant to vincristine, it was observed that the effect of nafoxidine on modulating drug resistance was manifested at a lower concentration than that causing a direct cytotoxic effect. Nafoxidine inhibited the Pgp pump activity as measured by rhodamine 123 efflux. Combination with verapamil was found to be more effective in abrogating the pump activity. This study points to the multifactorial activities of nonsteroidal antiestrogens against lymphoblastic leukemia and implies their potential use in clinical treatment as antileukemic drugs.
AB - The antileukemic activity of nonsteroidal antiestrogens was investigated. Tamoxifen, clomiphene and nafoxidine caused a decrease in viability of the estrogen receptor-negative T-lymphoblastic leukemia cell line CCRF/CEM, nafoxidine being the most active. A combination of clomiphene and genistein resulted in a synergistic cytotoxic effect when applied to Molt-3, another T-lymphblastic leukemic cell line. The antiestrogens arrested the cells at G0/G1 phase and induced apoptosis. Using the CCRF/VCR 1000 cell line, which is resistant to vincristine, it was observed that the effect of nafoxidine on modulating drug resistance was manifested at a lower concentration than that causing a direct cytotoxic effect. Nafoxidine inhibited the Pgp pump activity as measured by rhodamine 123 efflux. Combination with verapamil was found to be more effective in abrogating the pump activity. This study points to the multifactorial activities of nonsteroidal antiestrogens against lymphoblastic leukemia and implies their potential use in clinical treatment as antileukemic drugs.
KW - Apoptosis
KW - Drug resistance
KW - Nonsteroidal antiestrogens
KW - T-cell leukemia
UR - http://www.scopus.com/inward/record.url?scp=0242489233&partnerID=8YFLogxK
U2 - 10.1016/S0361-090X(03)00102-8
DO - 10.1016/S0361-090X(03)00102-8
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C2 - 14585326
AN - SCOPUS:0242489233
SN - 0361-090X
VL - 27
SP - 389
EP - 396
JO - Cancer Detection and Prevention
JF - Cancer Detection and Prevention
IS - 5
ER -