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Updated: Nov 10, 2025

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Pegylated Recombinant Human Arginase 1 Induces Autophagy and Apoptosis via the ROS-Activated AKT/mTOR Pathway in

Zhuyun Zhao1, Peng Zhang2, Wei Li3

  • 1Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, Guangdong, China.

Oxidative Medicine and Cellular Longevity
|April 1, 2021
PubMed

Insights

Recombinant human arginase (BCT-100) shows anticancer effects in bladder cancer by reducing arginine, inducing apoptosis and autophagy through the ROS-mediated AKT/mTOR pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Bladder cancer is a prevalent malignancy with limited therapeutic outcomes.
  • Current treatments for bladder cancer lack sufficient efficacy.
  • Recombinant human arginase (BCT-100) is a novel agent targeting arginine-auxotrophic tumors.

Purpose of the Study:

  • To investigate the anticancer effects of BCT-100 on bladder cancer.
  • To elucidate the mechanisms underlying BCT-100's action in bladder cancer cells.

Main Methods:

  • In vitro assessment using bladder cancer cell lines (J82, SCaBER, T24, 5637).
  • In vivo evaluation using T24 nude mice xenograft models.
  • Analysis of intracellular arginine levels, apoptosis, autophagy markers (LC3B, Beclin-1, p62), mitochondrial function, and AKT/mTOR pathway signaling.

Main Results:

  • BCT-100 significantly decreased intracellular arginine levels, triggering apoptosis.
  • BCT-100 induced reactive oxygen species (ROS) production and mitochondrial dysfunction.
  • BCT-100 promoted autophagy and suppressed the AKT/mTOR pathway.
  • N-acetyl-L-cysteine mitigated BCT-100 effects, while chloroquine, MK-2206, and rapamycin enhanced apoptosis.

Conclusions:

  • BCT-100 exhibits potent in vitro and in vivo anticancer activity against bladder cancer.
  • The mechanism involves ROS-mediated induction of apoptosis and autophagy via the AKT/mTOR pathway.
  • BCT-100 represents a promising therapeutic agent for bladder cancer treatment.

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