N-(4-hydroxyphenyl)retinamide activation of transforming growth factor- β and induction of apoptosis in human breast cancer cells

Brittney Shea Herbert, Bob G. Sanders, Kimberly Kline

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22 Scopus citations


N-(4 hydroxyphenyl)retinamide (4-HPR), a synthetic derivative of all- trans-retinoic acid, induces DNA synthesis arrest and apoptosis in human breast cancer cells in a dose- and time-dependent manner. MDA-MB-435 cells treated with 3 μM 4-HPR exhibited 58% and 75% DNA synthesis arrest after 1 and 2 days of treatment and 31%, 39%, 48%, and 56% apoptosis after 3, 4, 5, and 6 days of treatment, respectively. Conditioned media from 4-HPR-treated MDA-MB-435 cells contained 63 and 57 pg of active transforming growth factor- β (TGF-β) per 106 cells after 1 and 2 days of treatment, whereas conditioned media from control cells contained only 9 pg/106 cells. TGF-β involvement in 4-HPR- induced apoptosis, but not DNA synthesis arrest, in MDA-MB-435 cells was demonstrated by 1) blockage of 4-HPR-induced apoptosis by 66-75% after treatment of cells with neutralizing antibodies to TGF-βs, 2) blockage of 4-HPR-induced apoptosis by 64-67% after transient transfection of cells with antisense oligomers to TGF-β1 or TGF-β type H receptor, 3) blockage of 4-HPR-induced apoptosis by approximately 50% after inhibition of latent TGF-β activation, and 4) demonstration that human breast cancer cells (T47D) defective in TGF-β signaling were refractive to 4-HPR-induced apoptosis. These data indicate that 4-HPR is a potent activator of TGF-β and that TGF-β participates in 4-HPR-induced apoptosis of human breast cancer cells.

Original languageEnglish (US)
Pages (from-to)121-132
Number of pages12
JournalNutrition and Cancer
Issue number2
StatePublished - Jan 1 1999


ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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