Tanshinone IIA mediates SMAD7-YAP interaction to inhibit liver cancer growth by inactivating the transforming growth factor beta signaling pathway

Aging (Albany NY). 2019 Nov 11;11(21):9719-9737. doi: 10.18632/aging.102420. Epub 2019 Nov 11.

Abstract

Tanshinone IIA (TanIIA)-an active constituent of Salvia miltiorrhiza, a traditional Chinese medicinal plant-is known to have blood circulation promotion and anti-tumor properties. Tan IIA can induce tumor cell death and inhibit tumor growth. However, the functions and underling molecular mechanisms of Tan IIA action on human liver cancer cells remain poorly understand. In this study, we found that Tanshinone IIA mediates SMAD7-YAP interaction to induce liver cancer cell apoptosis and inhibit cell growth and migration by inactivating the transforming growth factor beta (TGF-β) signaling pathway. Our findings showed that the Tan IIA-SMAD7-YAP regulatory network might be an effective strategy for liver cancer treatment.

Keywords: HCC; SMAD7; TGF-β pathway; Tan IIA; YAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / pharmacology
  • Abietanes / therapeutic use*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinogenesis / drug effects
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Male
  • Middle Aged
  • Phytotherapy
  • Salvia miltiorrhiza*
  • Smad7 Protein / metabolism*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism
  • YAP-Signaling Proteins

Substances

  • Abietanes
  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Phytogenic
  • Drugs, Chinese Herbal
  • SMAD7 protein, human
  • Smad7 Protein
  • Transcription Factors
  • Transforming Growth Factor beta
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • tanshinone