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

Bin Yi, Hong Chang, Ruixia Ma, Xiangling Feng, Wei Li, Gary A. Piazza, Yaguang Xi

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 derivative of sulindac can inhibit breast tumor metastasis by a mechanism involving the TGFβ/miR-21 signaling axis.

Original languageEnglish (US)
Pages (from-to)7979-7992
Number of pages14
JournalOncotarget
Volume7
Issue number7
DOIs
StatePublished - Jan 1 2016

Fingerprint

Sulindac
Cell Movement
Breast Neoplasms
Prostaglandin-Endoperoxide Synthases
Neoplasms
Anti-Inflammatory Agents
Neoplasm Metastasis
Chemoprevention
Growth
MicroRNAs
Pharmaceutical Preparations
Prostaglandins
Carcinogenesis
Phosphorylation
sulindac sulfide amide
sulindac sulfide

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Inhibition of breast cancer cell motility with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFβ/miR-21 signaling. / Yi, Bin; Chang, Hong; Ma, Ruixia; Feng, Xiangling; Li, Wei; Piazza, Gary A.; Xi, Yaguang.

In: Oncotarget, Vol. 7, No. 7, 01.01.2016, p. 7979-7992.

Research output: Contribution to journalArticle

Yi, Bin ; Chang, Hong ; Ma, Ruixia ; Feng, Xiangling ; Li, Wei ; Piazza, Gary A. ; Xi, Yaguang. / Inhibition of breast cancer cell motility with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFβ/miR-21 signaling. In: Oncotarget. 2016 ; Vol. 7, No. 7. pp. 7979-7992.
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