Related Experiment Video

Updated: Jun 25, 2026

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

2-Methoxyestradiol mediated signaling network in pancreatic cancer

Aruna Basu1, Subrata Haldar

  • 1Center for Biomedical Sciences, Department of Pharmacology, Case Comprehensive Cancer Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, USA. abasu@metrohealth.org

Frontiers in Bioscience (Landmark Edition)
|March 11, 2009
PubMed

Insights

2-Methoxyestradiol (2-ME) suppresses pancreatic cancer growth by inducing apoptosis. This study identifies novel signaling proteins, including Glucocorticoid Receptor (GR) and NF-kappaB, involved in 2-ME

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • 2-Methoxyestradiol (2-ME), an endogenous 17 beta-estradiol metabolite, inhibits neovascularization and pancreatic tumor growth via apoptosis.
  • Understanding the precise molecular mechanisms of 2-ME action in pancreatic cancer is crucial for therapeutic development.

Purpose of the Study:

  • To elucidate novel signaling pathways modulated by 2-ME in pancreatic cancer.
  • To identify key proteins and their interactions in 2-ME-mediated anti-cancer effects.

Main Methods:

  • Utilized a PowerBlot Western Array screening system for proteomic profiling.
  • Analyzed protein expression changes in response to 2-ME in pancreatic cancer cells.
  • Investigated the interplay between Glucocorticoid Receptor (GR) and NF-kappaB signaling.

Main Results:

  • Identified novel 2-ME-responsive proteins including Rac1, Gelsolin, GR, Smad 2/3, Smad 4, and IRS-1.
  • Observed 2-ME-induced downregulation of GR correlated with NF-kappaB activation in sensitive cells.
  • Detected differential GR and NF-kappaB modulation between 2-ME-responsive and resistant pancreatic cancer cells.

Conclusions:

  • Proteomic profiling reveals new mechanisms of 2-ME action in pancreatic cancer.
  • A potential reciprocal relationship between GR and NF-kappaB activation may regulate 2-ME-induced apoptosis in a subset of pancreatic cancer cells.
  • These findings provide a framework for understanding 2-ME's therapeutic potential and resistance mechanisms in pancreatic cancer.

More Related Videos

Growing Desmoplastic Three-Dimensional Pancreatic Cancer Spheroids from Co-Culture03:42

Growing Desmoplastic Three-Dimensional Pancreatic Cancer Spheroids from Co-Culture

Published on: September 27, 2024

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...