Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA)

Leonard A. Cohen, Shantu Amin, Paul A. Marks, Richard A. Rifkind, Dhimant Desai, Victoria M. Richon

Research output: Contribution to journalArticle

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Abstract

Hybrid Polar Cytodifferentiation (HPC) agents represent a novel class of anticancer compounds which act by inducing terminal differentiation and/or apoptosis rather than by cytotoxic action. Among these are HPC agents such as hexamethylenebisacetamide (HMBA) and more potent 2nd generation hybrid/polar compounds such as suberanilohydroxamic acid (SAHA). As of the present, most studies on HPC agents have focused on cancers of the hematopoietic system rather than solid epithelial tumors. The objective of the present study therefore was to assess the chemopreventive action of these two related compounds in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Female Sprague-Dawley rats were fed diets containing 450 and 900 ppm, SAHA and 1000 and 2000 ppm HMBA, starting one week prior to NMU administration and continued for a period of 18 weeks. Mammary tumor development was monitored by palpation throughout the study, and at termination tumor incidence, number, multiplicity, latency and volume were determined. Weight gain was measured biweekly throughout the study. The salient results were as follows: SAHA at 900 ppm reduced NMU-induced mammary tumor incidence by 40%, total tumors by 66%, mean tumor multiplicity by 43% and mean tumor volume by 78%, with no detectable toxic side effects. HMBA exerted no tumor inhibiting effects at either concentration. This study represents the first demonstration that an HPC agent, namely SAHA, can inhibit the development of a chemically-induced solid epithelial tumor, at a relatively low dose (approximately 13 mgs/rat/day) without untoward side effects.

Original languageEnglish (US)
Pages (from-to)4999-5005
Number of pages7
JournalAnticancer Research
Volume19
Issue number6 B
StatePublished - Nov 1 1999

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Chemoprevention
Carcinogens
Carcinogenesis
Breast
Methylnitrosourea
Neoplasms
Breast Neoplasms
Hematopoietic System
Palpation
Poisons
Incidence
vorinostat
Tumor Burden
Weight Gain
Sprague Dawley Rats
Apoptosis
Diet

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cohen, Leonard A. ; Amin, Shantu ; Marks, Paul A. ; Rifkind, Richard A. ; Desai, Dhimant ; Richon, Victoria M. / Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). In: Anticancer Research. 1999 ; Vol. 19, No. 6 B. pp. 4999-5005.
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Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). / Cohen, Leonard A.; Amin, Shantu; Marks, Paul A.; Rifkind, Richard A.; Desai, Dhimant; Richon, Victoria M.

In: Anticancer Research, Vol. 19, No. 6 B, 01.11.1999, p. 4999-5005.

Research output: Contribution to journalArticle

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T1 - Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA)

AU - Cohen, Leonard A.

AU - Amin, Shantu

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AU - Richon, Victoria M.

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