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Updated: Jun 21, 2026

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Published on: March 17, 2020

Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of

Terry W Moody¹, Christopher Switzer, Wilmarie Santana-Flores

¹National Cancer Institute, Office of the Director, Center for Cancer Research, Bethesda, MD 20892-1500, USA. moodyt@mail.nih.gov

Lung Cancer (Amsterdam, Netherlands)

|July 25, 2009

Summary

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Cadherins in Tissue Organization

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
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This summary is machine-generated.

Modified valproate and diclofenac, known as S-valproate and S-diclofenac, show promise in inhibiting non-small cell lung cancer (NSCLC) growth and reducing prostaglandin E2 levels. These compounds may be beneficial for NSCLC chemoprevention and therapy.

Area of Science:

Oncology
Pharmacology
Cancer Research

Background:

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
Prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) are implicated in NSCLC development and progression.
Novel therapeutic strategies targeting these pathways are needed for effective NSCLC treatment.

Purpose of the Study:

To investigate the effects of dithiolethione-modified valproate, diclofenac, and sulindac on NSCLC cells.
To evaluate the potential of these modified drugs in NSCLC chemoprevention and therapy.
To elucidate the mechanisms underlying their anti-cancer effects in NSCLC.

Main Methods:

In vitro studies using NSCLC cell lines (A549, NCI-H1299) to assess cell growth inhibition and PGE2 levels.

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Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Published on: March 17, 2020

In vivo xenograft models in nude mice to evaluate tumor proliferation.

MTT assays and Western blot analysis to determine mechanisms of action, including apoptosis, E-cadherin, vimentin, and ZEB1 expression.

Main Results:

S-valproate and S-diclofenac significantly reduced PGE2 levels in NSCLC cells.
In vitro, S-valproate and S-diclofenac inhibited clonal growth of NSCLC cells.
In vivo, S-valproate and S-diclofenac suppressed xenograft tumor proliferation without affecting body weight.
These agents modulated E-cadherin, vimentin, and ZEB1 protein expression.

Conclusions:

S-valproate and S-diclofenac demonstrate significant anti-proliferative effects on NSCLC cells in vitro and in vivo.
The reduction in PGE2 levels and modulation of key proteins suggest a potential therapeutic role.
These modified drugs may be valuable agents for the chemoprevention and/or therapy of NSCLC.