Latcripin-7A from Lentinula edodes C91-3 induces apoptosis, autophagy, and cell cycle arrest at G1 phase in human gastric cancer cells via inhibiting PI3K/Akt/mTOR signaling

Eur J Pharmacol. 2021 Sep 15:907:174305. doi: 10.1016/j.ejphar.2021.174305. Epub 2021 Jul 2.

Abstract

Gastric cancer (G.C) is one of the most lethal cancer types worldwide. Current treatment requires surgery along with chemotherapy, which causes obstacles for speedy recovery. The discovery of novel drugs is needed for better treatment of G.C with minimum side effects. Latcripin-7A (LP-7A) is a newly discovered peptide extracted from Lentinula edodes. It is recently studied for its anti-cancer activity. In this study, LP-7A was modeled using a phyre2 server. Anti-proliferation effects of LP-7A on G.C cells were examined via CCK-8, colony formation, and morphology assay. Apoptosis of LP-7A treated G.C cells was evaluated via Hoechst Stain, western blot and flow cytometry. Autophagy was assessed via acridine orange staining and western blot. The cell cycle was assessed via flow cytometry assay and western blot. Pathway was studied via western blot and STRING database. Anti-migratory effects of LP-7A treated G.C cells were analyzed via wound healing, western blot, and migration and invasion assay. LP-7A effectively inhibited the growth of G.C cells by inhibiting the PI3K/Akt/mTOR pathway. G.C cells treated with LP-7A arrested the cell cycle at the G1 phase, contributing to the inhibition of migration and invasion. Furthermore, LP-7A induced apoptosis and autophagy in gastric cancer cells. These results indicated that LP-7A is a promising anti-cancer agent. It affected the proliferation and growth of G.C cells (SGC-7901 and BGC-823) by inducing apoptosis, autophagy, and inhibiting cell cycle at the G1 phase in G.C cells.

Keywords: Apoptosis; Autophagy; Gastric cancer; Latcripin-7A; Lentinula edodes; PI3K/Akt/mTOR.

MeSH terms

  • Autophagy / drug effects
  • Humans
  • Phosphatidylinositol 3-Kinases*
  • Proto-Oncogene Proteins c-akt
  • Shiitake Mushrooms
  • Signal Transduction / drug effects
  • Stomach Neoplasms
  • TOR Serine-Threonine Kinases

Substances

  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases