Evaluation of the effect of the new methoxy-stilbenes on expression of receptors and enzymes involved in estrogen synthesis in cancer breast cells

• Published in: Molecular and cellular biochemistry 2018-07, Vol.444 (1-2), p.53-62
• Main Authors: Licznerska, Barbara, Szaefer, Hanna, Wierzchowski, Marcin, Mikstacka, Renata, Papierska, Katarzyna, Baer-Dubowska, Wanda
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Aromatase; Basic Helix-Loop-Helix Transcription Factors - biosynthesis; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer treatment; Cardiology; Cell culture; Cells; Chemical synthesis; Cytochrome P-450; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P450; Drug Screening Assays, Antitumor; Enzymes; Estradiol; Estrogen Receptor alpha - biosynthesis; Estrogen receptors; Estrogens; Estrogens - biosynthesis; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Life Sciences; MCF-7 Cells; Medical Biochemistry; Metabolism; Metastases; Neoplasm Proteins - biosynthesis; Neurons; Oncology; Phenols (Class of compounds); Proteins; Receptors; Receptors, Aryl Hydrocarbon - biosynthesis; Recombinant proteins; Resveratrol; RNA; Sex hormones; Stilbene; Stilbenes - chemistry; Stilbenes - pharmacology; trans-Stilbene; Transcription; Tumor cell lines
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-017-3230-7

Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2′-trimethoxy- trans -stilbene (3MS), 3,4,2′,4′-tetramethoxy- trans -stilbene (4MS), and 3,4,2′,4′,6′-pentamethoxy- trans -stilbene (5MS), modulate the constitutive expression of enzymes and receptors involved in estrogen metabolism in breast immortalized epithelial MCF10 cells. In this study, we evaluated the effect of 3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen-dependent and MDA-MB-231 estrogen-independent breast cancer cell lines. 3MS similarly to resveratrol reduced the expression of estrogen receptor α in MCF7 cells. However, in these cells, 5MS reduced the most CYP19 , the gene encoding aromatase, at mRNA transcript level. In contrast, in the MDA-MB-231 cells, the most efficient inhibitor of CYP19 expression was 3MS, reducing the level of its protein by ~ 25%. This stilbene also inhibited the aromatase activity in a recombinant protein system with IC 50 value ~ 85 µM. Treatment with the methoxy-stilbenes reduced the level of estradiol in culture medium. The most significant reduction was exerted by 3MS. None of the tested stilbenes including resveratrol changed significantly the expression of AhR, although CYP1A1 protein level was slightly reduced in MDA-MB-231 cells, while CYP1B1 expression was increased in these cells as a result of treatment with 3MS, but only at the transcript level. Overall, these results show weak or moderate effect of the new methoxy-stilbenes on the expression of key proteins involved in estrogens metabolism in cancer breast cells. However, the reduced CYP19 expression and activity upon 3MS treatment in metastatic MDA-MB-231 cells require the further studies.