Nimbolide Exhibits Potent Anticancer Activity Through ROS-Mediated ER Stress and DNA Damage in Human Non-small Cell Lung Cancer Cells

The non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. It is usually diagnosed at an advanced stage with poor prognosis. Nimbolide (NB), a terpenoid limonoid isolated from the flowers and leaves of neem tree, possesses anticancer properties in various cancer cell lines. However, the underlying mechanism of its anticancer effect on human NSCLC cells remains unclear. In the present study, we investigated the effect of NB on A549 human NSCLC cells. We found that NB treatment inhibits A549 cells colony formation in a dose-dependent manner. Mechanistically, NB treatment increases cellular reactive oxygen species (ROS) level, leading to endoplasmic reticulum (ER) stress, DNA damage, and eventually induction of apoptosis in NSCLC cells. Furthermore, all these effects of NB were blocked by pretreatment with antioxidant glutathione (GSH), the specific ROS inhibitor. We further knockdown CHOP protein by siRNA markedly reduced NB-induced apoptosis in A549 cells. Taken together, our findings reveal that NB is an inducer of ER stress and ROS; these findings may contribute to increasing the therapeutic efficiency of NSCLC.

Automated summary

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of all cases. Nimbolide (NB), a compound derived from the neem tree, has been shown to exhibit anti-cancer properties in various types of cancer cells. In this study, the researchers investigated the effect of NB on A549 human NSCLC cells and found that NB treatment inhibited the colony formation of these cells in a dose-dependent manner. The mechanism behind this anti-cancer effect was found to involve the induction of cellular reactive oxygen species (ROS), resulting in endoplasmic reticulum (ER) stress, DNA damage, and ultimately apoptosis in the NSCLC cells.