𝔖 Bobbio Scriptorium
✦   LIBER   ✦

2-Methoxyestradiol modulates β-catenin in prostate cancer cells: A possible mediator of 2-methoxyestradiol-induced inhibition of cell growth

✍ Scribed by Peter J. Van Veldhuizen; Gibanananda Ray; Snigdha Banerjee; Gopal Dhar; Suman Kambhampati; Animesh Dhar; Sushanta K. Banerjee

Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
235 KB
Volume
122
Category
Article
ISSN
0020-7136

No coin nor oath required. For personal study only.

✦ Synopsis

2-Methoxyestradiol (2-ME 2 ) is a novel anticancer agent because of its ability to potentiate apoptotic cell death and inhibit cancer cell growth and angiogenesis. The modes of action of this agent, however, have not yet been fully elucidated. In our study, we have investigated whether 2-ME2 is able to modulate b-catenin signaling in prostate cancer cells, which is one of the major players in cell-cell adhesion, proliferation, apoptosis and carcinogenesis. We found that b-catenin levels were significantly upregulated by 2-ME 2 in a dose-dependent manner in androgen dependent and independent prostate cancer total cellular extracts. We further show that b-catenin levels were significantly increased in the membrane fraction, while nuclear fractions of b-catenin were downregulated in the 2-ME 2 -treated cells. Accumulation of dephospho-b-catenin (nondegraded form) parallel with Bcl-2 and Cyclin D1 downregulation was also achieved after 2-ME 2 treatment. Moreover, we demonstrate that the b-catenin production by 2-ME 2 is mediated through the MEK/ERK-2 signaling pathway. Collectively, these results suggest that the cytostatic effect of 2-ME 2 may be mediated through the prevention of the translocation of b-catenin to the nucleus parallel with an increase in cell-cell adhesion by increasing membrane b-catenin production, eventually preventing cell migration. Moreover, dephospho-b-catenin accumulation by 2ME 2 in the cytoplasm may contribute to the induction of apoptosis of these cells. Finally, studies testing the efficacy of 2-ME 2 in human prostate cancer are warranted to determine whether the inhibition of the expected loss of membranous b-catenin and the upregulation of nuclear b-catenin can prevent prostate cancer development and progression.

📜 SIMILAR VOLUMES

2-methoxyestradiol blocks cell-cycle pro
2-methoxyestradiol blocks cell-cycle progression at G2/M phase and inhibits growth of human prostate cancer cells
✍ Addanki P. Kumar; Gretchen E. Garcia; Thomas J. Slaga 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 English ⚖ 358 KB 👁 1 views

## Abstract 2‐Methoxyestradiol (2‐ME), an endogenous metabolite of 17β‐estradiol, is present in human blood and urine. Here we show for the first time that 2‐ME significantly inhibited the growth of normal prostate epithelial cells and androgen‐dependent LNCaP and androgen‐independent DU145 prostat

Mechanism of 2-methoxyestradiol-induced
Mechanism of 2-methoxyestradiol-induced apoptosis and growth arrest in human breast cancer cells
✍ Masayuki Fukui; Bao Ting Zhu 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 496 KB 👁 1 views

## Abstract 2‐Methoxyestradiol, a well‐known nonpolar endogenous metabolite of 17β‐estradiol, has been shown to selectively induce apoptosis in a number of cancer cell lines, but not in normal cells. The mechanism of 2‐methoxyestradiol‐induced apoptosis appears to vary considerably in different cel

The molecular mechanism of sensitization
The molecular mechanism of sensitization to Fas-mediated apoptosis by 2-methoxyestradiol in PC3 prostate cancer cells
✍ Keiji Shimada; Mitsutoshi Nakamura; Eiwa Ishida; Munehiro Kishi; Syuchi Matsuyos 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 301 KB

## Abstract It is widely known that death receptor Fas‐dependent apoptotic signals are associated with development of prostate cancer, but the key pathways involved in sensitivity to the apoptosis remain unclear. Here we investigated the molecular mechanism by which 2‐methoxyestradiol (2‐ME) effect

Inhibition of Wnt-2 and galectin-3 syner
Inhibition of Wnt-2 and galectin-3 synergistically destabilizes β-catenin and induces apoptosis in human colorectal cancer cells
✍ Yihui Shi; Biao He; Kristopher M. Kuchenbecker; Liang You; Zhidong Xu; Iwao Mika 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 French ⚖ 336 KB

## Abstract Constitutive activation of the Wnt pathway as a result of __APC__, __AXIN1__ or __CTNNB1__ mutations has been found in most colorectal cancers. For a long time, this aberrant Wnt activation has been thought to be independent of upstream signals. However, recent studies indicate that ups

Involvement of ATM-mediated Chk1/2 and J
Involvement of ATM-mediated Chk1/2 and JNK kinase signaling activation in HKH40A-induced cell growth inhibition
✍ Ziqiu Wang; Meifang Wang; Sid Kar; Brian I. Carr 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 308 KB

## Abstract HKH40A (RTA 502), or 5‐nitro‐2‐(3‐{4‐[3‐(8‐methoxy‐6‐oxo‐6H‐2,10b‐diaza‐aceanthrylen‐5‐ylamino)propyl]piperazin‐1‐yl}‐propyl)‐2‐aza‐phenalene‐1,3‐dione, has been shown to be a potent cell growth inhibitor. To investigate HKH40A actions, we focused on exploring the signal transduction pa

Does endogenous fatty acid metabolism al
Does endogenous fatty acid metabolism allow cancer cells to sense hypoxia and mediate hypoxic vasodilatation? Characterization of a novel molecular connection between fatty acid synthase (FAS) and hypoxia-inducible factor-1α (HIF-1α)-related expression of vascular endothelial growth factor (VEGF) in cancer cells overexpressing her-2/neu oncogene
✍ Javier A. Menendez; Luciano Vellon; Bharvi P. Oza; Ruth Lupu 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 English ⚖ 249 KB 👁 1 views

## Abstract Her‐2/__neu__ (__erb__B‐2) oncogene overexpression is associated with increased tumor progression and metastasis. Fatty acid synthase (FAS), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, has been shown to be one of the genes regulated by Her‐2/__neu__