Multifactorial activities of nonsteroidal antiestrogens against leukemia

Tamar Hayon, Lena Atlas, Etti Levy, Alexander Dvilansky, Ofer Shpilberg, Ilana Nathan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Pages (from-to)389-396
Number of pages8
JournalCancer Detection and Prevention
Issue number5
StatePublished - 2003
Externally publishedYes


  • Apoptosis
  • Drug resistance
  • Nonsteroidal antiestrogens
  • T-cell leukemia


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