Combined effect of baicalein and thermal-cycling stimulation on suppressing non-small cell lung cancer A549 cells under CoCl2-induced hypoxia

Non-small cell lung cancer (NSCLC) remains the most common form of lung cancer, responsible for the majority of cancer-related deaths worldwide. A hallmark of NSCLC is tumor hypoxia, which enables tumor growth and renders the cancer resistant to oxidative stress via the stabilization of hypoxia-inducible factor-1 alpha (HIF-1). To explore potential therapeutic strategies, researchers examined the combined effects of baicalein (Bai), a natural flavonoid, and thermal-cycling stimulation (TCS), a physical treatment that avoids harming healthy cells, in A549 NSCLC cells exposed to cobalt (II) chloride (CoCl2)-induced hypoxia.

Under hypoxic conditions, the simultaneous administration of Bai and TCS led to a significant reduction in A549 cell viability and triggered apoptosis. Importantly, this combined therapy showed minimal toxicity towards IMR-90 normal human lung fibroblast cells. Mechanistically, Bai and TCS worked together to suppress HIF-1 and superoxide dismutase 2 (SOD2) protein expression, increase intracellular reactive oxygen species (ROS) levels, and impair DNA repair by lowering MutT homolog 1 (MTH1) protein levels.

Furthermore, the treatment disrupted mitochondrial membrane potential and elevated poly (ADP-ribose) polymerase (PARP) cleavage, both of which are indicators of apoptosis.

The combined impact of Bai and TCS suggests a promising synergistic approach to combating NSCLC under hypoxic conditions, offering a potential new avenue for cancer treatment.