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Multifactorial activities of nonsteroidal antiestrogens against leukemia.

Cancer detection and prevention (2003-10-31)
Tamar Hayon, Lena Atlas, Etti Levy, Alexander Dvilansky, Ofer Shpilberg, Ilana Nathan
ABSTRACT

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 G(0)/G(1) 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nafoxidine hydrochloride, ≥98% (HPLC)

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