Carnosol enhances radiosensitivity in NSCLC cells by targeting the miR-17-5p/TOLLIP/NF-κB Axis

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Radiotherapy resistance is a major challenge in treating non-small cell lung cancer (NSCLC).
• Novel therapeutic strategies are needed to overcome radioresistance in NSCLC.
• Natural compounds are being explored for their potential in cancer therapy.

Purpose of the Study:

• To investigate the radiosensitizing effects of carnosol, a rosemary-derived diterpene, in NSCLC.
• To elucidate the molecular mechanisms underlying carnosol's action, focusing on the miR-17-5p/TOLLIP/NF-κB axis.
• To evaluate carnosol's impact on cancer cell viability, apoptosis, and DNA repair.

Main Methods:

• A549 NSCLC cells were treated with carnosol and X-ray irradiation.
• Cell viability and apoptosis were assessed using CCK-8 and TUNEL assays.
• DNA damage, gene/protein expression, and pathway interactions were analyzed via comet, qRT-PCR, Western blotting, and dual-luciferase assays.

Main Results:

• Carnosol downregulated miR-17-5p and upregulated TOLLIP, suppressing TLR4 and p-NF-κB p65 while increasing IκBα.
• These molecular changes impaired DNA repair mechanisms (increased γH2AX, decreased RAD51).
• Carnosol significantly enhanced radiation-induced apoptosis and reduced clonogenic survival in NSCLC cells (P < 0.01).

Conclusions:

• Carnosol exhibits radiosensitizing properties in NSCLC by modulating the miR-17-5p/TOLLIP/NF-κB signaling pathway.
• The compound disrupts DNA repair pathways, contributing to its ability to overcome radioresistance.
• Carnosol demonstrates significant therapeutic potential for enhancing radiotherapy efficacy in NSCLC patients.