Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA) Journal Article
| Authors: | Cohen, L. A.; Amin, S.; Marks, P. A.; Rifkind, R. A.; Desai, D.; Richon, V. M. |
| Article Title: | Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA) |
| 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. |
| Keywords: | controlled study; unclassified drug; nonhuman; cancer incidence; animal cell; animals; breast cancer; tumor volume; animal experiment; animal model; cell differentiation; dose-response relationship, drug; anticarcinogenic agents; rat; hydroxamic acids; rats; rats, sprague-dawley; breast carcinogenesis; mammary neoplasms, experimental; carcinogen; carcinogens; weight gain; methylnitrosourea; hydroxamic acid derivative; hexamethylenebisacetamide; acetamides; female; priority journal; article; mammary tumor; suberanilohydroxamic acid; hexamethylene bis acetamide (hmba); histone deacetylase (hdac) inhibitor; n-methylnitrosourea (nmu); suberanilo-hydroxamic acid (saha) |
| Journal Title: | Anticancer Research |
| Volume: | 19 |
| Issue: | 6B |
| ISSN: | 0250-7005 |
| Publisher: | International Institute of Anticancer Research |
| Date Published: | 1999-11-01 |
| Start Page: | 4999 |
| End Page: | 5005 |
| Language: | English |
| PUBMED: | 10697502 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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