In this work, we addressed the effects of H. alpestre and L-NAME on the PI3K/Akt/mTOR-mediated changes in A549 lung adenocarcinoma and MDA-MB-231 triple-negative breast cancer cell cultures by elucidating the roles of the tumor necrosis factor-alpha (TNFα)/cyclooxygenase-2 (COX-2) and vascular endothelial growth factor A (VEGFα)/matrix metalloproteinase-2 (MMP-2) tandems. This evidence concerns the gene PTGS2 and lung adenocarcinoma.