F41, a Novel Fungal Indole-Diterpenoid, Overcomes Gemcitabine Resistance in Pancreatic Cancer by Inducing ER Stress.

Pancreatic cancer is an aggressive malignancy with a poor prognosis. It is characterized by low surgical resection rates, frequent development of chemoresistance, unsatisfactory treatment outcomes, and a high potential for recurrence and metastasis. Compound F41, a naturally occurring indole-diterpenoid secondary metabolite, was isolated from the entomopathogenic fungus Penicillium sp. Its anti-pancreatic cancer activity has not been previously reported. Our study demonstrates that F41 significantly inhibits DNA replication, invasion, and proliferation in pancreatic cancer cells. By elevating intracellular reactive oxygen species (ROS) levels in pancreatic cancer cells, F41 induces endoplasmic reticulum stress, ultimately leading to apoptosis. These findings suggest that F41 could effectively overcome gemcitabine resistance in a clinical setting, indicating its promise as a potential therapeutic agent for pancreatic cancer.