Furanodienone inhibits cell proliferation and survival by suppressing ERα signaling in human breast cancer MCF-7 cells

Ying Wei Li, Guo Yuan Zhu, Xiao Ling Shen, Jian Hong Chu, Zhiling YU, David W F FONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Estrogen receptor alpha (ERα) plays an important role in the development and progression of breast cancer and thus the attenuation of ERα activities is a promising treatment strategy. Furanodienone is one of the main bioactive chemical components of Rhizoma Curcumae which is commonly used in Chinese medicine for the treatment of cancer. In this study, we investigated the effects of furanodienone on human breast cancer MCF-7, T47D, and MDA-MB-231 cells. Our results showed that furanodienone could inhibit MCF-7, T47D, and MDA-MB-231 cells proliferation in a dose (10-160 μM) dependent manner. ERa-negative MDA-MB-231 cells were less sensitive to furanodienone than ERα-positive MCF-7 and T47D cells. Furanodienone could effectively block 17β-estradiol (E2)-stimulated MCF-7 cell proliferation and cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1 DNA content and the appearance of apoptotic nuclei after DAPI staining. Furanodienone specifically down-regulated ERα protein and mRNA expression levels without altering ERβ expression. Furanodienone treatment inhibited E2-stimulation of estrogen response element (ERE)-driven reporter plasmid activity and ablated E2- targeted gene (e.g., c-Myc, Bcl-2, and cyclin D1) expression which resulted in the inhibition of cell cycle progression and cell proliferation, and in the induction of apoptosis. Knockdown of ERα in MCF-7 cells by ERα-specific siRNA decreased the cell growth inhibitory effect of furanodienone. These findings suggest that effects of furanodienone on MCF-7 cells are mediated, at least in part, by inhibiting ERa signaling.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalJournal of Cellular Biochemistry
Volume112
Issue number1
DOIs
Publication statusPublished - Jan 2011

Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

User-Defined Keywords

  • Breast cancer
  • Estrogen receptor alpha
  • Furanodienone
  • MCF-7

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