Decursin Induces G1 Cell Cycle Arrest and Apoptosis through Reactive Oxygen Species-Mediated Endoplasmic Reticulum...

Area of Science:

• Pharmacology
• Molecular Biology
• Oncology

Background:

• Decursin, a coumarin from Angelica gigas, shows anti-inflammatory and anti-cancer potential.
• The precise anti-cancer mechanisms of decursin in human colorectal cancer (CRC) remain largely unelucidated.
• Understanding decursin's action is crucial for developing novel CRC therapeutics.

Purpose of the Study:

• To investigate the anti-cancer biological activities of decursin against human colorectal cancer (CRC) cell lines in vitro.
• To elucidate the molecular mechanisms underlying decursin's anti-tumor effects, focusing on cell cycle regulation, apoptosis, and stress pathways.
• To evaluate decursin's efficacy and safety in a preclinical in vivo model of CRC.

Main Methods:

• In vitro studies utilized HCT-116 and HCT-8 human colorectal cancer cells to assess decursin's effects on cell cycle progression, apoptosis, and reactive oxygen species (ROS) production.
• The role of ROS in decursin-induced apoptosis was confirmed using the antioxidant N-acetyl-L-cysteine.
• In vivo efficacy was evaluated in a subcutaneous xenograft mouse model, assessing tumor growth, cell proliferation (Ki-67), and apoptosis markers (cleaved caspase 3).

Main Results:

• Decursin demonstrated significant anti-tumor activity in vitro, inducing G1 cell cycle arrest and apoptosis in CRC cells.
• Decursin triggered ROS production, which activated the endoplasmic reticulum (ER) stress apoptotic pathway; inhibition of ROS reversed these effects.
• In vivo, decursin suppressed tumor growth in xenograft models without observable host toxicity, reducing proliferation and increasing apoptosis markers via ER stress activation.

Conclusions:

• Decursin effectively induces cell cycle arrest and apoptosis in human colorectal cancer cells.
• The anti-cancer mechanism involves the generation of ROS, leading to ER stress-induced apoptosis.
• Decursin shows promise as a potential therapeutic agent for colorectal cancer, warranting further clinical investigation.