ABSTRACT
OBJECTIVE: The proposed therapeutical effect of phytol (PHY), a precursor of the phytanic acid (PHYA), on mammary tumours induced with 1-methyl-1-nitrosourea (MNU), was investigated in Sprague-Dawley rats in combination with vitamin D analogue, Seocalcitol (SEO). METHODS: Female Sprague-Dawley rats were administered intraperitoneally with MNU (50 mg/kg of body weight) at the 46th and 52th days of age. Controls and MNU animals received propyleneglycol appropriate to their body weight. PHY (MNU + PHY) (500 mg/kg) was administered after tumour detection (approximately in 100th day of the life) three times/week. Combination of PHY with SEO (7 µg/kg per week) was administered to rats after tumour detection (approximately in 100th day of the life) until the 181st day of age. Then the animals were sacrificed, the tumours removed, and fixed in 10% formalin. Haematoxylin and eosine stained sections were evaluated under microscope. RESULTS: Tumour invasiveness observed in all groups of animals was ranging from 80 to 90%. Treatment with PHY alone did not inhibit the progression of the MNU induced tumours in the rat breast but it decreased the tumour burden and volume in comparison with MNU treated controls. Decreased tumour burden and volume were induced by combined treatment of PHY with SEO. Malignity and invasivity of carcinomas were not affected. CONCLUSION: No redifferentiating effect on mammary tumour cells induced by NMU after treatment with PHY alone or in combination with SEO was observed in rats. SEO alone or in combination with PHY inhibited the progression of MNU induced mammary tumours and also inhibited the increase of tumour burden and volume in comparison with MNU treated control group. However, none of the compounds, either alone or in mutual combination, reduced the malignity or the number of invasive tumours in this experimental study.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/pathology , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Alkylating Agents , Animals , Carcinoma/chemically induced , Disease Progression , Drug Evaluation, Preclinical , Female , Mammary Neoplasms, Experimental/chemically induced , Methylnitrosourea , Phytanic Acid/administration & dosage , Phytanic Acid/analogs & derivatives , Phytanic Acid/chemistry , Rats , Rats, Sprague-Dawley , Tumor Burden/drug effects , Vitamin D/administration & dosage , Vitamin D/analogs & derivativesABSTRACT
In the present work, the effects of colchicine (COL) and/or all-trans retinoic acid (ATRA) on expression of rexinoid receptors (RXRs) (alpha, beta, gamma), thyroid hormone receptor alpha and coregulators N-CoR, SMRT and SRC-1 mRNA in primary rat hepatocytes as a model of no-proliferating cells were investigated. Treatment with these components, either alone or in combination, induced differences of the expression profiles between distinct treatment groups.
Subject(s)
Colchicine/administration & dosage , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Retinoic Acid/metabolism , Receptors, Thyroid Hormone/metabolism , Repressor Proteins/metabolism , Tretinoin/administration & dosage , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Drug Interactions , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , RatsABSTRACT
Dihydroxyvitamin D(3) is known to affect broad spectrum of various biochemical and molecular biological reactions in organisms. Research on the role and function of nuclear vitamin D(3) receptors (VDR) playing a role as dihydroxyvitamin D(3) inducible transcription factor belongs to dynamically developing branches of molecular endocrinology. In higher organisms, full functionality of VDR in the form of heterodimer with nuclear 9-cis retinoic acid receptor is essential for biological effects of dihydroxyvitamin D(3). This article summarizes selected effects of biologically active vitamin D(3) acting through their cognate nuclear receptors, and also its potential use in therapy and prevention of various types of cancer.