4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells

Journal Article · Wed Jun 15 04:00:00 EDT 2016 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2016.03.003· OSTI ID:22689182

Ronghe, Amruta; Chatterjee, Anwesha ^[1]; Singh, Bhupendra ^[2]; Dandawate, Prasad ^[3]; Abdalla, Fatma; Bhat, Nimee K. ^[1]; Padhye, Subhash ^[3]

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1. Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States)
2. Department of Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
3. ISTRA, Department of Chemistry, Abeda Inamdar Senior College, University of Pune (India)

Breast cancer is a public health concern worldwide. Prolonged exposure to estrogens has been implicated in the development of breast neoplasms. Epidemiologic and experimental evidence suggest a chemopreventive role of phytoestrogens in breast cancers. Resveratrol, a naturally occurring phytoestrogen, has been shown to have potent anti-cancer properties. However, poor efficacy and bioavailability have prevented the use of resveratrol in clinics. In order to address these problems, we have synthesized a combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the proliferation of breast cancer cells. We have recently shown that 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), has better anti-cancer properties than resveratrol and any other resveratrol analog we have synthesized so far. The objective of this study was to investigate the regulation of estrogen receptors (ERs) α and β by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERβ and inhibits that of ERα. TIMBD inhibits mRNA and protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, which are important regulators of cellular proliferation. TIMBD significantly induces protein expression levels of tumor suppressor genes p53 and p21 in MCF-7 cells. TIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10 A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERβ plays a partial role in inhibition of proliferation by TIMBD while ERα overexpression does not significantly affect TIMBD's inhibition. - Highlights: • Resveratrol analog TIMBD inhibits growth of breast cancer cells. • TIMBD induces protein expression levels of ERβ and inhibits that of ERα. • TIMBD inhibits c-Myc and cyclin D1, and induces p53 and p21. • TIMBD suppresses c-Myc in an ER-dependent fashion.

• OSTI ID: 22689182
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 301; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL AVAILABILITY
CELL CYCLE
CELL PROLIFERATION
ESTROGENS
GLYCOLS
INHIBITION
MAMMARY GLANDS
MESSENGER-RNA
MONOCLINIC LATTICES
NEOPLASMS
ONCOGENES
PUBLIC HEALTH
RECEPTORS
TOLUENE