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Gamabufotalin inhibits colitis-associated colorectal cancer by suppressing transcription factor STAT3

Nian Jiang1, Sanhua Li1, Lingjie Meng1

  • 1Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi Guizhou, 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou, 563000, China.

European Journal of Pharmacology
|February 1, 2024
PubMed

Insights

Gamabufotalin (Gam) effectively inhibits colorectal cancer (CRC) by inducing apoptosis and suppressing STAT3. This compound shows promise for preventing CRC and colitis-associated cancer (CAC) development.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is crucial in colorectal cancer (CRC) pathogenesis.
  • STAT3 inhibition is a potential therapeutic strategy for CRC.
  • Gamabufotalin (Gam), a compound from ChanChu, has shown therapeutic potential with good metabolic stability and low adverse effects, but its role in CRC is not well-defined.

Purpose of the Study:

  • To investigate the effect of Gamabufotalin (Gam) on colorectal cancer (CRC) in vitro and in vivo.
  • To determine if Gamabufotalin (Gam) can inhibit cancer cell viability and induce apoptosis by targeting STAT3.
  • To evaluate Gamabufotalin's (Gam) efficacy in preventing colitis-associated cancer (CAC) in a mouse model.

Main Methods:

  • In vitro studies using HCT-116 and HT-29 cell lines to assess cell viability and apoptosis.
  • In vivo studies using an AOM/DSS mouse model to evaluate the effect on colitis-associated cancer (CAC).
  • Analysis of STAT3 signaling pathway inhibition by Gamabufotalin (Gam).

Main Results:

  • Gamabufotalin (Gam) significantly inhibited CRC cell viability in a dose-dependent manner.
  • Gamabufotalin (Gam) induced apoptosis in HCT-116 and HT-29 cells by suppressing STAT3.
  • Gamabufotalin (Gam) demonstrated efficacy in inhibiting colitis-associated cancer (CAC) development in the AOM/DSS mouse model by targeting STAT3.

Conclusions:

  • Gamabufotalin (Gam) exhibits significant anti-cancer properties against colorectal cancer (CRC) and colitis-associated cancer (CAC).
  • The mechanism involves the induction of apoptosis and suppression of the STAT3 signaling pathway.
  • Gamabufotalin (Gam) represents a potential therapeutic agent for the prevention and treatment of CRC and CAC.
Keywords:
Colitis-associated colorectal cancerColorectal cancerGamabufotalinSTAT3

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