Pterostilbene inhibits non-small cell lung cancer progression by activating the STING pathway and enhancing antitumor...

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) presents a significant global health challenge with limited therapeutic options.
• Pterostilbene (PTE), a natural stilbenoid, possesses enhanced bioavailability and warrants investigation for its potential anticancer properties.

Purpose of the Study:

• To investigate the antitumor efficacy of Pterostilbene (PTE) in non-small cell lung cancer (NSCLC) models.
• To elucidate the molecular mechanisms underlying PTE's anticancer effects, including its impact on cell death and the tumor immune microenvironment.

Main Methods:

• In vitro studies utilized NSCLC cell lines (A549, H358) to assess cell viability, cell cycle, apoptosis, and reactive oxygen species (ROS) generation.
• Molecular mechanisms were explored using Western blot, siRNA, and pharmacological inhibitors.
• In vivo efficacy was evaluated in H358 xenograft and LLC1 murine models, including analysis of the tumor immune microenvironment.

Main Results:

• PTE demonstrated dose- and time-dependent suppression of NSCLC cell viability, inducing G2/M phase arrest and ROS-mediated mitochondrial apoptosis.
• PTE activated the STING pathway, promoting DNA damage and secretion of T-cell chemoattractants, which was abrogated by STING inhibition.
• In vivo, PTE reduced tumor growth and modulated the immune microenvironment by increasing cytotoxic CD8+ T cells and decreasing immunosuppressive cells.

Conclusions:

• PTE exhibits a dual mechanism of action: direct cytotoxicity via ROS-mediated apoptosis and immune system activation through the STING pathway.
• PTE represents a promising therapeutic candidate for NSCLC, particularly in combination with immunotherapy strategies.