Tanshinone IIA inhibits endometrial carcinoma growth through the MAPK/ERK/TRIB3 pathway

Arch Biochem Biophys. 2023 Jul 15:743:109655. doi: 10.1016/j.abb.2023.109655. Epub 2023 Jun 5.

Abstract

Endometrial carcinoma is the most common gynecological tumor in developed countries. Tanshinone IIA is a traditional herbal medicine which is to treat cardiovascular disease and has been shown to have various biological effects, such as anti-inflammatory, antioxidative and antitumor activities. However, there has been no study about the effect of tanshinone IIA on endometrial carcinoma. Thus, the aim of this study was to determine the antitumor activity of tanshinone IIA against endometrial carcinoma and investigate the associated molecular mechanism. We demonstrated that tanshinone IIA induced cell apoptosis and inhibited migration. We further demonstrated that tanshinone IIA activated the intrinsic (mitochondrial) apoptotic pathway. Mechanistically, tanshinone IIA induced apoptosis by upregulating TRIB3 expression and inhibiting the MAPK/ERK signaling pathway. In addition, knockdown of TRIB3 with an shRNA lentivirus accelerated proliferation and attenuated inhibition mediated by tanshinone IIA. Finally, we further demonstrated that tanshinone IIA inhibited tumor growth by inducing TRIB3 expression in vivo. In conclusion, these findings suggest that tanshinone IIA has a significant antitumor effect by inducing apoptosis and may be used as a drug for the treatment of endometrial carcinoma.

Keywords: Cell apoptosis; Endometrial carcinoma; Tanshinone IIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes* / pharmacology
  • Abietanes* / therapeutic use
  • Apoptosis
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Endometrial Neoplasms* / drug therapy
  • Female
  • Humans
  • Protein Serine-Threonine Kinases
  • Repressor Proteins

Substances

  • tanshinone
  • Abietanes
  • TRIB3 protein, human
  • Repressor Proteins
  • Protein Serine-Threonine Kinases
  • Cell Cycle Proteins