Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl₂-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl₂) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC₅₀ of 12 μg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1β and downstream genes was strongly suppressed in the presence of CA in CoCl₂-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.