Antiproliferative Effect of Rosmarinic Acid in Non-Small Cell Lung Cancer Stem Cells

Non-small cell lung cancer (NSCLC) stem cells play a crucial role in cancer recurrence and therapy resistance due to their self-renewal, differentiation, invasion, and metastatic abilities. Therefore, eliminating NSCLC stem cells is considered a potent tactic to improve the efficacy of NSCLC treatment. Rosmarinic acid (RA) is a naturally occurring compound belonging to the multifunctional phenolic family, present in various plants. In this study, the inhibitory activity of RA on the proliferation ability of NSCLC stem cells was evaluated. The results showed that RA significantly inhibited the proliferation and tumorsphere formation ability of NSCLC stem cells derived from HCC827 and NCI-H1650. Particularly, the inhibitory effect of RA on the proliferation of both NSCLC stem cells was attributed to cell cycle arrest at G0/G1 phase and induction of apoptosis. Moreover, molecular mechanism analysis revealed that RA’s inhibitory activity on NSCLC stem cell proliferation was linked to blocking the activation of the EGFR signaling pathway and reducing the expression of key stem cell markers. These findings underscore the potential of RA as a natural remedy for the prevention and treatment of NSCLC.