Bellidifolin Inhibits Proliferation of A549 Cells by Regulating STAT3/COX-2 Expression and Protein Activity

Area of Science:

• Pharmacology
• Oncology
• Natural Products Chemistry

Background:

• Bellidifolin (BEL), a xanthone from Gentianaceae, exhibits diverse pharmacological activities.
• Its potential in lung cancer treatment remains largely unexplored.
• This study investigates BEL's antiproliferative effects on A549 lung cancer cells.

Purpose of the Study:

• To evaluate the antiproliferative and cytotoxic effects of Bellidifolin (BEL) on A549 lung cancer cells.
• To elucidate the underlying molecular mechanisms using network pharmacology and in vitro assays.
• To identify potential therapeutic targets for BEL in lung cancer treatment.

Main Methods:

• Cellular experiments (CCK8 assays, H&E staining, cell cycle analysis, Western blot) were used to assess BEL's effects on A549 cells.
• Network pharmacology, utilizing TCMSP and STRING databases, identified potential molecular targets.
• In vitro analysis and molecular docking were performed to validate core targets (STAT3, COX-2).

Main Results:

• BEL demonstrated significant, dose- and time-dependent inhibition of A549 cell proliferation without affecting normal lung cells.
• BEL induced nuclear condensation, S/G2 phase arrest, and apoptosis (increased caspase-8/3, decreased PARP1).
• Network pharmacology identified STAT3 and COX-2 as key targets, with BEL potentially acting via the STAT3/COX-2 pathway.

Conclusions:

• Bellidifolin exhibits potent antiproliferative and cytotoxic effects against A549 lung cancer cells.
• The mechanism involves targeting the STAT3/COX-2 pathway, leading to apoptosis.
• This research supports BEL as a candidate for novel lung cancer phytotherapy development.