Furanodienone

Furanodienone inhibits cell proliferation and survival by suppressing ERalpha signaling in human breast cancer MCF-7 cells.[Pubmed:21069738]

J Cell Biochem. 2011 Jan;112(1):217-24.

Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of breast cancer and thus the attenuation of ERalpha 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 microM) dependent manner. ERalpha-negative MDA-MB-231 cells were less sensitive to Furanodienone than ERalpha-positive MCF-7 and T47D cells. Furanodienone could effectively block 17beta-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 ERalpha protein and mRNA expression levels without altering ERbeta 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 ERalpha in MCF-7 cells by ERalpha-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 ERalpha signaling.

Furanodienone induces cell cycle arrest and apoptosis by suppressing EGFR/HER2 signaling in HER2-overexpressing human breast cancer cells.[Pubmed:21461888]

Cancer Chemother Pharmacol. 2011 Nov;68(5):1315-23.

PURPOSE: Overexpression of EGFR and HER2 is seen in breast cancers and results in poor prognosis and decreased patient survival. Clinically, EGFR and HER2 are effective therapeutic targets. The objective of this study is to investigate the in vitro effects of Furanodienone, an active chemical component isolated from Rhizoma Curcumae, on the activation of EGFR/HER2 signaling, cell cycle, and apoptosis in HER2-overexpressing BT474 and SKBR3 cells. METHODS: Cell growth was assessed by SRB protein assay. Cell cycle analysis was carried out by flow cytometry, and apoptosis was observed by Annexin V and DAPI staining. Effects of Furanodienone on the activation of EGFR/HER2 signaling-related proteins were analyzed by western blotting. RESULTS: Furanodienone inhibited cell growth in BT474 and SKBR3 cells. Furanodienone caused G1 arrest in BT474 cells and induced apoptosis in SKBR3 cells. Furanodienone interfered with EGFR/HER2 signaling in treated cells as shown by decreases in phosphorylated EGFR, HER2, Akt, Gsk3beta and an increase in p27(kip1) protein. Accordingly, Furanodienone inhibited EGF-induced phosphorylation of EGFR, HER2, Akt, and Gsk3beta. EGFR-specific siRNA knockdown did not affect the cell growth inhibitory effect of Furanodienone. On the contrary, specific siRNA knockdown of HER2 increased cellular resistance to Furanodienone toxicity. In HER-2-deficient MDA-MB-231 cells, the transfection and expression of HER2 increased the sensitivity of cells to Furanodienone toxicity. CONCLUSION: Furanodienone inhibited EGFR/HER2 signaling pathway in BT474 and SKBR3 cells. More importantly, the effect of Furanodienone was specifically dependent on HER2, but not EGFR, expression.