Globularifolin Exerts Anticancer Effects on Human Lung Cancer Cells Via Regulation of ROS and Suppression of PINK1/Parkin Mitophagy Pathway

Objectives: In the present study, the in vitro anticancer effects of globularifolin were evaluated against human lung cancer and attempts were made to explore the underlying molecular mechanisms. Materials and Methods: Cell viability and proliferation was determined by MTT, EdU, and colony formation assays. Cellular processes were detected by annexin V/PI, confocal microscopy and flow cytometry. Protein expression was detected by western blotting. Results: The results showed that globularifolin suppressed the growth and colony formation of the human lung cancer cells and exhibited an IC50 of 8 µM against the HCC827 and SK‑LU‑1 lung cancer cell lines. However, the IC50 of globularifolin was found to be comparatively higher against the normal MRC‑5 cells. The globularifolin‑induced inhibition of human lung cancer cells were found to be due to the induction of apoptosis, which was associated with upregulation of Bax, caspase‑3 and caspase‑9, and downregulation of Bcl‑2. Further investigation of the underlying mechanism revealed that inhibitory effects of globularifolin were mediated through apoptotic induction driven through inhibition of PI3K/Akt and PINK/ Parkin signaling pathways driven respectively through reactive oxygen species (ROS) production and mitophagy. Conclusion: Taken together, the results show that globularifolin exerts anticancer effects on human lung cancer cells via regulation of ROS and suppression of PINK1/Parkin mitophagy pathway.