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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.
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.
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