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Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway

Chaozheng Zhang1, Yuening Cao1, Yi Zuo1

  • 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Frontiers in Pharmacology
|April 14, 2023
PubMed

Insights

Bruceine A (BA) shows promise as a colon cancer (CC) chemotherapy drug. It inhibits CC cell proliferation, migration, and induces apoptosis by targeting the PI3K/Akt pathway.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Bruceine A (BA), a quassin ester from *bruceine javanica*, exhibits diverse biological activities.
  • The precise pharmacological mechanism of BA in treating colon cancer (CC) remains largely unelucidated.
  • Understanding BA's action is crucial for developing novel CC therapeutics.

Purpose of the Study:

  • To investigate the anticancer effects of Bruceine A (BA) on colon cancer (CC) cells.
  • To elucidate the underlying molecular mechanisms of BA's anti-CC activity.

Main Methods:

  • Network pharmacology to identify key targets and pathways (Akt1, Jun, PI3K/Akt).
  • Molecular docking to predict BA's interaction with PI3K/Akt pathway proteins.
  • In vitro assays (proliferation, Western blot, cell cycle analysis, apoptosis assays) on CC cell lines (HCT116, CT26).

Main Results:

  • BA significantly suppressed proliferation of HCT116 and CT26 cells.
  • BA downregulated p-PI3K and p-Akt expression, indicating PI3K/Akt pathway inhibition.
  • BA induced G2 cell cycle arrest, promoted apoptosis via Bax activation and ROS accumulation, and inhibited cell migration.

Conclusions:

  • Bruceine A exerts potent anti-colon cancer effects by targeting the PI3K/Akt signaling pathway.
  • BA modulates cell cycle progression, induces apoptosis, and inhibits migration in CC cells.
  • BA demonstrates potential as a novel chemotherapeutic agent for colon cancer treatment.
Keywords:
Bruceine A (BA)PI3K/AKTapoptosiscolon cancermolecular docknetwork pharmacology

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