Inhibition of breast cancer cell motility with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFβ/miR-21 signaling

Oncotarget
Bin YiYaguang Xi

Abstract

Compelling efficacy on intervention of tumorigenesis by nonsteroidal anti-inflammatory drugs (NSAIDs) has been documented intensively. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for human cancer chemoprevention. A novel derivative of the NSAID sulindac sulfide (SS), referred as sulindac sulfide amide (SSA), was recently developed, which lacks COX inhibitory activity, yet shows greater suppressive effect than SS on growth of various cancer cells. In this study, we focus on the inhibitory activity of SSA on breast tumor cell motility, which has not been studied previously. Our results show that SSA treatment at non-cytotoxic concentrations can specifically reduce breast tumor cell motility without influencing tumor cell growth, and the mechanism of action involves the suppression of TGFβ signaling by directly blocking Smad2/3 phosphorylation. Moreover, miR-21, a well-documented oncogenic miRNA for promoting tumor cell metastasis, was also found to be involved in inhibitory activity of SSA in breast tumor cell motility through the modulation of TGFβ pathway. In conclusion, we demonstrate that a non-COX inhibitory d...Continue Reading

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Citations

Jul 31, 2020·Journal of Biochemical and Molecular Toxicology·Fatma AbdallaHari K Bhat
Oct 11, 2020·Acta Pharmacologica Sinica·Xiaolin LiuYaguang Xi

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Methods Mentioned

BETA
nuclear translocation
scraping
transfection
ChIP
pull-down
PCR
xenograft
Assay
protein assay
Confocal

Software Mentioned

Elements AR
NIS
GraphPad Prism
EVOS

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