3,5,3′,4′,5′ -Pentamethoxystilbene (MR-5), a synthetically methoxylated analogue of resveratrol, inhibits growth and induces G1 cell cycle arrest of human breast carcinoma MCF-7 Cells

Min Hsiung Pan, Chih L.I. Lin, Jie Heng Tsal, Chi Tang Ho, Wei Jen Chen

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

3,5,3′,4′,5′ -Pentamethoxystilbene (MR-5) is a synthetically methoxylated analogue of resveratrol and has been suggested to have antitumor activity because of structural similarity to resveratrol. Herein, we investigate the antiproliferative effect of MR-5 in human breast cancer MCF-7 cells and demonstrate that MR-5 had a more potent inhibition on cell growth compared with resveratrol and other methoxylated derivatives. Exploring the growth-inhibitory mechanisms of MR-5, we found that it is accompanied by G1 cell cycle arrest, which coincides with a marked inhibition of G1 cell cycle regulatory proteins, including decreased cyclins (D1/D3/E) and cyclin-dependent kinases (CDK2/4/6) and increased CDK inhibitors (CKIs) such as p15, p16, p21, and p27. Furthermore, the increase in CKI levels by MR-5 resulted In a concomitant increase in their interactions of CDK4 and CDK2, along with a strong inhibition in CDK4 kinase activity and the accumulation of hypophosphorylated Rb. MR-5 also modulated some critical kinase activities related to cell cycle regulation, including Akt, mitogenactivated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), and focal adhesion kinase (FAK) in MCF-7 cells. In total, our results demonstrate that MR-5 affects multiple cellular targets that contribute to its antiproliferative activity in MCF-7 cells and provide novel information for synthetic chemists to design new antitumor agents with introduction of methoxylated group(s) in the basic compound.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalJournal of agricultural and food chemistry
Volume58
Issue number1
DOIs
StatePublished - Jan 13 2010

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • 3,5,3′,4′,5′ -pentamethoxystilbene (MR-5)
  • CDK inhibitors (CKIS)
  • Cell cycle
  • Cyclins
  • Cyclln-dependent kinases (CDKS)
  • G1 arrest
  • Resveratrol

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