The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor 13-dependent apoptosis in breast cancer

Mara H. Rendi, Nanjoo Suh, William W. Lamph, Stan Krajewski, John C. Reed, Richard A. Heyman, Andrew Berchuck, Karen Liby, Renee Risingsong, Darlene B. Royce, Charlotte R. Williams, Michael B. Sporn

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

We show that the selective estrogen receptor modulator arzoxifene (Arz) and the rexinoid LG100268 (268) synergize to promote apoptosis in a rat model of estrogen receptor-positive breast carcinoma and in estrogen receptor-positive human breast cancer cells in culture. We also show that it is not necessary to administer Arz and 268 continuously during tumor progression to prevent cancer in the rat model because dosing of these drugs in combination for relatively short periods, each followed by drug-free rests, is highly effective. This new approach to chemoprevention uses high doses of drugs that are too toxic for long-term administration. However, when given for short periods, the agents are nontoxic and still induce apoptosis in breast cancer cells. We also show that the ability of the two drugs to induce apoptosis is the combined result of induction of transforming growth factor β by Arz, together with inhibition of the prosurvival nuclear factor κB and phosphatidylinositol 3′ kinase signaling pathways by 268. The new protocol we have developed for chemoprevention allows the efficacious and safe administration of 268 and Arz, and these agents now should be considered for clinical use.

Original languageEnglish (US)
Pages (from-to)3566-3571
Number of pages6
JournalCancer Research
Volume64
Issue number10
DOIs
StatePublished - May 15 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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