Arnicolide D inhibits triple negative breast cancer cell proliferation by suppression of akt/mTOR and STAT3 signaling pathways

Zhao Qu, Yushan Lin, Daniel Kam Wah Mok, Qingya Bian, William Chi Shing Tai (Corresponding Author), Sibao Chen (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Triple-Negative Breast Cancer (TNBC) is a most dangerous breast cancer subtype. The naturally occurring sesquiterpene lactone, arnicolide D (AD), has proven effective against a variety of tumors, however, the inhibitory effects of AD against TNBC and the underlying mechanisms remain unclear. In the present study, two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and an MDA-MB-231 xenograft mouse model were employed to investigate the anti-TNBC effects of AD in vitro and in vivo. Cell viability was assessed by MTT assay. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by immunoblotting. In vitro studies demonstrated that AD significantly decreased cell viability, and induced G2/M cell cycle arrest and apoptosis. In vivo assays showed that oral administration of 25 or 50 mg/kg AD for 22 days led to a reduction of tumor weights by 24.7% or 41.0%, without appreciable side effects. Mechanistically, AD inhibited the activation of Akt/mTOR and STAT3 signaling pathways. Based on our findings, AD is a promising candidate for development as an adjunctive therapeutic drug for TNBC.

Original languageEnglish
Pages (from-to)1482-1490
Number of pages9
JournalInternational Journal of Medical Sciences
Volume17
Issue number11
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Akt/mTOR
  • Arnicolide D
  • STAT3
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Medicine(all)

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