Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway

Abstract

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.