Selection of a highly tumorigenic breast cancer cell line sensitive to estradiol to evidence in vivo the tumor-inhibitory effect of butyrate derivative monobut-3

• Published in: Life sciences (1973) Vol. 55; no. 12; pp. 951 - 959
• Main Authors: Planchon, P., Magnien, V., Starzec, A., Prevost, G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1994
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; breast cancer cells; Breast Neoplasms - drug therapy; butyrate derivative; Butyrates - pharmacology; Butyrates - therapeutic use; Carcinoma, Ductal, Breast - drug therapy; Cell Division - drug effects; Estradiol - metabolism; estrogen receptor; Female; Glucose - analogs & derivatives; Glucose - pharmacology; Glucose - therapeutic use; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Hormone-Dependent - drug therapy; Receptors, Estrogen - analysis; tumor bearing mice; Tumor Cells, Cultured; butyrate derivative; breast cancer cells; tumor bearing mice; estrogen receptor
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(94)00541-9

To increase butyric acid mean residence time in vivo, we have produced a stable butyric acid derivative, Monobut-3. Recently, we have described that Monobut-3 is able to induce phenotypic changes in human mammary tumor cells in vitro. In this study, we explore the in vivo effect of Monobut-3. Human breast tumor cell-lines did not easily produce in vivo xenografts, thus, MCF-7 cells required exogenous 17β-estradiol to grow and to form in vivo xenografts. To evaluate in vivo anti-tumor effects of monobut-3 without exogenous 17β-estradiol addition, we have established MCF-7 variant cells, highly tumorigenic MCF-7vht, in which transfection of rats oncogene induced a bypass of estrogen requirement but did not delete the presence of functional estrogen receptor (ER). Monobut-3 inhibited growth of this variant by about 90% at 4 mM and reduced 17β-estradiol cell growth stimulation. In vivo, in absence of 17β-estradiol, 2 mg per mouse monobut-3 decreased tumor take by about 25% and tumor growth by about 50% in nude mice. This is the first experimental demonstration of an in vivo antitumoral effect of a butyric acid derivative alone on a solid human tumor. These data suggest that this compound does not only act by reducing of 17β-estradiol stimulation but it also has an 17β-estradiol-independent effect. Absence of toxicity and its antiproliferative effects could suggest its use in clinical treatment of well differentiated carcinoma.