Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells via the ROS‑regulated MAPK, STAT3 and NF‑κB signaling pathways.

Abstract

Isoorientin (ISO) is a naturally occurring C‑glycosyl flavone that has various pharmacological properties, such as anti‑bacterial and anti‑inflammatory effects. However, its underlying molecular mechanisms in human lung cancer cells remain unknown. In the present study, the effects of ISO on the induction of apoptosis and relative molecular mechanisms in A549 human lung cancer cells were investigated. The results of Cell Counting Kit‑8 assay (CCK‑8) indicated that ISO exerted significant cytotoxic effects on 3lung cancer cell lines, but had no obvious side‑effects on normal cells. Moreover, flow cytometry and western blot analysis revealed that ISO induced mitochondrial‑dependent apoptosis by reducing mitochondrial membrane potential. ISO also increased the expression levels of Bax, cleaved‑caspase‑3 (cle‑cas‑3) and poly(ADP‑ribose) polymerase (PARP; cle‑PARP), and decreased the expression levels of Bcl‑2 in A549 cells. Furthermore, ISO induced G2/M cell cycle arrest by decreasing the expression levels of cyclin B1 and CDK1/2, and increasing the expression levels of p21 and p27 in A549 cells. As the duration of ISO treatment increased, intracellular reactive oxygen species (ROS) levels in A549 cells also increased. However, pre‑treatment of the cells with the ROS scavenger, N‑acetylcysteine (NAC), inhibited ISO‑induced apoptosis. In addition, ISO increased the expression levels of p‑p38, p‑JNK and IκB‑α; and decreased the expression levels of p‑extracellular signal‑regulated kinase (ERK), p‑signal transducer and activator of transcription (STAT)3, p‑nuclear factor (NF)‑κB, NF‑κB and p‑IκB; these effects were induced by mitogen‑activated protein kinase (MAPK) inhibitors and blocked by NAC. Taken together, the results of the present study indicate that ISO induces the apoptosis of A549 lung cancer cells via the ROS‑mediated MAPK/STAT3/NF‑κB signaling pathway, and thus may be a potential drug for use in the treatment of lung cancer.