4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors alpha and beta in breast cancer cells.
Article Details
- CitationCopy to clipboard
Ronghe A, Chatterjee A, Singh B, Dandawate P, Abdalla F, Bhat NK, Padhye S, Bhat HK
4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors alpha and beta in breast cancer cells.
Toxicol Appl Pharmacol. 2016 Jun 15;301:1-13. doi: 10.1016/j.taap.2016.03.003. Epub 2016 Mar 9.
- PubMed ID
- 26970359 [ View in PubMed]
- Abstract
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) alpha and beta by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERbeta and inhibits that of ERalpha. 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 ERbeta-dependent fashion in MCF-10A and ERbeta1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERbeta plays a partial role in inhibition of proliferation by TIMBD while ERalpha overexpression does not significantly affect TIMBD's inhibition.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions 2-Methoxy-6-{(E)-[(4-methylphenyl)imino]methyl}phenol Estrogen receptor alpha Protein Humans UnknownNot Available Details 2-Methoxy-6-{(E)-[(4-methylphenyl)imino]methyl}phenol Estrogen receptor beta Protein Humans UnknownNot Available Details - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Resveratrol Investigational CCND1 595 downregulated resveratrol analog results in decreased expression of CCND1 mRNA 11q13.3 Resveratrol Investigational ESR1 2099 downregulated resveratrol analog results in decreased expression of ESR1 mRNA 6q25.1-q25.2 Resveratrol Investigational ESR1 2099 downregulated resveratrol results in decreased expression of ESR1 mRNA 6q25.1-q25.2 Resveratrol Investigational ESR2 2100 upregulated resveratrol analog results in increased expression of ESR2 mRNA 14q23.2-q23.3 Resveratrol Investigational ESR2 2100 upregulated resveratrol results in increased expression of ESR2 mRNA 14q23.2-q23.3 Resveratrol Investigational MYC 4609 downregulated resveratrol analog results in decreased expression of MYC mRNA 8q24.21