Formosanin C Induces ROS/p38-Mediated Cell Death While Also Promoting Protective Autophagy in Pancreatic Cancer

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options.
• Formosanin C (FC) exhibits anti-inflammatory and anti-cancer properties.
• The efficacy of FC against PDAC remains largely unexplored.

Purpose of the Study:

• To evaluate the anti-PDAC effects of Formosanin C (FC).
• To elucidate the underlying molecular mechanisms of FC action in PDAC.

Main Methods:

• Cell proliferation assays (CCK8, colony formation, EDU, cell cycle)
• Apoptosis assessment (Annexin V-FITC/PI)
• Reactive Oxygen Species (ROS) detection (DCFH-DA)
• Western blot and immunocytochemistry for protein expression
• In vivo xenograft model for antitumorigenic activity evaluation

Main Results:

• FC suppressed PDAC cell proliferation and induced DNA damage.
• FC triggered apoptosis linked to endoplasmic reticulum (ER) stress and ROS generation.
• ROS were critical for FC-induced cell death, involving p38 pathway activation.
• FC induced cytoprotective autophagy, and blocking autophagy enhanced FC's anti-proliferative effect.
• In vivo studies confirmed FC's inhibition of PDAC tumor growth.

Conclusions:

• FC exhibits significant anti-PDAC activity by inducing ROS/p38-mediated cell death.
• FC also stimulates a cytoprotective autophagy, suggesting a dual role.
• FC presents a promising therapeutic candidate for pancreatic ductal adenocarcinoma.