Schisandrin B exhibits potent anticancer activity in triple negative breast cancer by inhibiting STAT3

Toxicol Appl Pharmacol. 2018 Nov 1:358:110-119. doi: 10.1016/j.taap.2018.09.005. Epub 2018 Sep 5.

Abstract

Triple negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. In this study, we have examined the potential of Schisandrin B (Sch B), a bioactive chemical compound found in Schisandra chinensis, against TNBC. We used MDA-MB-231, BT-549, and MDA-MB-468 TNBC cells and immunodeficient mice to study the effect of Sch B. Our results show that Sch B inhibits TNBC growth by inducing cell cycle arrest and by triggering apoptotic death. Sch B also inhibited the migration and colony formation of tumor cells, and prevented the growth of TNBC cells in mice. We found that these inhibitory activities were mediated through suppression of signal transducer and activator of transcription-3 (STAT3) phosphorylation and nuclear translocation. Taken together, our studies show that Sch B has potent anti-tumor activity against TNBC via a novel mechanism involving STAT3 inactivation.

Keywords: Apoptosis; STAT3; Schisandrin B; Triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cyclooctanes / pharmacology
  • Cyclooctanes / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Polycyclic Compounds / pharmacology*
  • Polycyclic Compounds / therapeutic use
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism*
  • Tumor Burden / drug effects
  • Tumor Burden / physiology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Cyclooctanes
  • Lignans
  • Polycyclic Compounds
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • schizandrin B