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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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
Volume34
Issue number2
StatePublished - 1999
Externally publishedYes

Fingerprint

Fenretinide
transforming growth factors
Transforming Growth Factors
breast neoplasms
apoptosis
Apoptosis
Breast Neoplasms
cells
synthesis
Conditioned Culture Medium
DNA
neoplasm cells
retinoic acid
transfection
neutralizing antibodies
Growth Factor Receptors
Tretinoin
Neutralizing Antibodies
chemical derivatives
Transfection

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Food Science

Cite this

N-(4-hydroxyphenyl)retinamide activation of transforming growth factor- β and induction of apoptosis in human breast cancer cells. / Herbert, Brittney-Shea; Sanders, Bob G.; Kline, Kimberly.

In: Nutrition and Cancer, Vol. 34, No. 2, 1999, p. 121-132.

Research output: Contribution to journalArticle

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abstract = "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.",
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