p53 independent G0/G1 arrest and apoptosis induced by a novel retinoid in human breast cancer cells

Oncogene. 1995 Aug 3;11(3):493-504.


The biological activity of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) was investigated in human breast carcinoma (HBC) cells. Although capable of selective binding to the RAR gamma nuclear receptor, AHPN inhibited the growth of a number of HBC cell lines via RAR- or RXR-independent pathways. AHPN also inhibited the growth of the human leukemia cell line HL-60R which does not possess functional RARs. RA significantly inhibited AP-1 mediated gene activation in MCF-7 cells while AHPN displayed no such anti-AP-1 activity. Retinoids normally are cytostatic in their inhibition of breast carcinoma growth and permit cell proliferation upon their removal, wher as AHPN induced G0/G1 arrest within 6h followed by apoptosis. In MCF-7 cells that harbor wild type p53, AHPN-induced G0/G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels while bcl-2 mRNA levels were decreased. In MDA-MB-231 cells which possess a mutant p53, AHPN-mediated G0/G1 arrest and apoptosis was also associated with a concomitant up regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus AHPN represents a novel retinoid that induces G0/G1 arrest and apoptosis via a unique pathway which appears to involve activation of known downstream effectors of p53 in a p53-independent manner.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA Damage
  • Gene Expression Regulation, Neoplastic / drug effects
  • Growth Inhibitors*
  • Humans
  • In Vitro Techniques
  • Naphthalenes / pharmacology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger / genetics
  • Retinoids / pharmacology*
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology
  • bcl-2-Associated X Protein


  • BAX protein, human
  • CD 437
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Growth Inhibitors
  • Naphthalenes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Retinoids
  • Transcription Factor AP-1
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein