Musk ketone induces apoptosis of gastric cancer cells via downregulation of sorbin and SH3 domain containing 2

Mol Med Rep. 2021 Jun;23(6):450. doi: 10.3892/mmr.2021.12089. Epub 2021 Apr 21.

Abstract

Musk ketone exerts antiproliferative effects on several types of cancer, such as lung and breast cancer. However, the effects and underlying mechanisms of action of musk ketone in gastric cancer (GC) are poorly understood. The present study aimed to investigate the effects of musk ketone in GC cells. The present study indicated that musk ketone exerted significant anticancer effects on GC cells. The IC50 values of musk ketone were 4.2 and 10.06 µM in AGS and HGC‑27 cells, respectively. Low dosage of musk ketone significantly suppressed the proliferation and colony formation of AGS and HGC‑27 cells. Cell cycle arrest and apoptosis were induced by musk ketone. Furthermore, microarray data indicated that musk ketone treatment led to downregulation of various genes, including sorbin and SH3 domain containing 2 (SORBS2). Reverse transcription‑quantitative PCR and immunoblotting results indicated that musk ketone repressed mRNA and protein expression levels of SORBS2. It was also shown that knockdown of SORBS2 inhibited the proliferation and colony formation of HGC‑27 cells. The antiproliferative effects of musk ketone were decreased in HGC‑27 cells with SORBS2 silencing. In summary, the present study indicated that musk ketone suppressed the proliferation and growth of GC partly by downregulating SORBS2 expression.

Keywords: musk ketone; gastric cancer; cell cycle; apoptosis; sorbin and SH3 domain containing 2.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • RNA, Messenger
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Stomach
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Xylenes / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • RNA, Messenger
  • RNA-Binding Proteins
  • SORBS2 protein, human
  • Xylenes
  • musk ketone

Grants and funding

The present study was supported by grants from the Applied Basic Research of Qinghai (grant no. 2018-ZJ-744), the CAS (Light of the West China) Program (grant no. 2019-33), the National Natural Science Foundation of China (grant no. 81460429), the Open Project of State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University (grant no. 2019-ZZ-07) and the Chunhui Plan of Ministry of Education of China (grant no. Z2017037).