Differential Effects of Olive Leaf Extract on Human Small and Non-Small Cell Lung Cancer and Synergy with Cisplatin: Rationale for Its Potential Use as Food Supplement for Patients?

Lung cancer is classified as either Non-Small Cell (NSCLC) and Small Cell Lung Cancer (SCLC) and still represents the leading cause of cancer-related mortality worldwide. Prognosis of NSCLC and SCLC patients is grim; thus, novel therapies are needed. In this context, plant-derived compounds, such as olive leaf extract (OLE), recently attracted much interest for their anti-cancer properties. We investigated the impact of OLE on cell proliferation and apoptosis (by flow cytometry) and migration (by scratch test and transwell assay) of NSCLC and SCLC cell lines, underlying the mechanisms involved. Synergistic effects with cisplatin were also evaluated. OLE differentially impaired cell proliferation and induced apoptosis in LC cell lines. Notably, such effects were higher in SCLC than in NSCLC cell lines. Further analyses were performed on GLC-1 and SKMES cells, identified as OLE-sensitive and OLE-resistant models, respectively. Indeed, OLE triggered the intrinsic apoptotic pathway by activating cleaved caspase-9, -3 and -7, and induced DNA damage response and cellular stress molecules in GLC-1 cells only. In contrast, OLE affected migratory capacity of SKMES cell line and modulated stress adaptation and survival pathways. Finally, OLE synergized with cisplatin in the induction of apoptosis in GLC-1 cells. OLE exerted multiple anti-tumor effects on LC cells in vitro. Its ability to enhance cisplatin-induced apoptosis supports further investigation of OLE as a potential dietary adjunct to chemotherapy. Although OLE has an established safety profile, in vivo studies are required to validate its efficacy, and assess potential interactions with chemotherapeutic drugs before any clinical application.