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Actein enhances TRAIL effects on suppressing gastric cancer progression by activating p53/Caspase-3 signaling

Zhi-Chao Yang1, Ji Ma1

  • 1Huaihe Hospital of Henan University, Southern Institute of Huaihe Hospital of Henan University, No. 8 Hubei Road, 475000 Henan, China.

Biochemical and Biophysical Research Communications
|December 5, 2016
PubMed

Insights

Actein (ACT) enhances TRAIL therapy for gastric cancer. Combining ACT with TRAIL synergistically induces apoptosis and inhibits tumor growth without toxicity, offering a new therapeutic strategy.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Actein (ACT), a triterpene glycoside from Cimicifuga foetida, shows promise in breast cancer.
  • The therapeutic potential of ACT in gastric cancer remains largely unexplored.

Purpose of the Study:

  • To investigate the in vitro and in vivo effects of ACT on gastric cancer.
  • To explore the synergistic interaction between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gastric cancer cells.

Main Methods:

  • In vitro assays to assess apoptosis induction and protein expression.
  • In vivo mouse xenograft model to evaluate tumor growth inhibition.
  • Analysis of apoptosis-related proteins, including Caspases, Bcl-2 family members, and decoy receptors.

Main Results:

  • Gastric cancer cells were insensitive to TRAIL monotherapy but sensitive when combined with ACT.
  • ACT sensitized cells to TRAIL by upregulating decoy receptors (DcR1 and DcR2) dependent on p53, enhancing Caspase cleavage.
  • Combined ACT and TRAIL treatment decreased anti-apoptotic proteins (Bcl-2, Mcl-1) and increased pro-apoptotic proteins (Bad, Bak).
  • In vivo, combination therapy significantly inhibited gastric cancer growth without observed toxicity.

Conclusions:

  • ACT acts synergistically with TRAIL to induce apoptosis and inhibit gastric cancer growth.
  • This combination therapy represents a promising strategy for gastric cancer treatment by enhancing TRAIL-induced anti-cancer effects.
Keywords:
ActeinCaspasesGastric cancerTRAILp53

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