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4-Phenylbutyric Acid Reduces the Proliferation in Colon Cancer Cell Lines Through Modulating the Cell Cycle

Dikshita Deka1, Alakesh Das1, Nabajyoti Baildya2

  • 1Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India.

Cancer Reports (Hoboken, N.J.)
|September 15, 2025
PubMed
Abstract

Insights

4-phenylbutyric acid (4-PBA) reduces endoplasmic reticulum stress (ER-stress) and inflammation in colon cancer. This compound exhibits anti-inflammatory and anticarcinogenic properties, offering potential for new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Endoplasmic reticulum stress (ER-stress) is implicated in cancer development and progression.
  • Research focuses on chemical chaperones to mitigate ER-stress.

Purpose of the Study:

  • Investigate 4-phenylbutyric acid (4-PBA) effects on colon cancer cell proliferation and inflammation.
  • Examine 4-PBA's role in regulating ER-stress-related protein expression.

Main Methods:

  • Molecular docking and dynamics simulations to assess 4-PBA binding with ER-stress proteins (IRE1-α, PDI, GRP78, PERK, NRF2).
  • Quantified expression of ER-stress, pro-inflammatory, and cell-cycle genes.
  • Measured inflammatory proteins, catalase, and reactive oxygen species (ROS) levels in colon cancer cells treated with 4-PBA.

Main Results:

  • In silico analysis revealed strong binding of 4-PBA to IRE1-α and PERK.
  • 4-PBA treatment downregulated ER-stress, cell-cycle, and pro-inflammatory genes.
  • Reduced pro-inflammatory proteins, ROS, and increased catalase indicate a link between ER-stress and inflammation.

Conclusions:

  • 4-PBA demonstrates anti-inflammatory and anticarcinogenic effects in colon cancer.
  • Findings suggest 4-PBA as a potential therapeutic agent for cancer treatment.
Keywords:
4‐phenylbutyric acidER‐stressdockingintestinal inflammationmolecular dynamics simulationunfolded protein responses

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