Chemosensitization Effect of Seabuckthorn (Hippophae rhamnoides L.) Pulp Oil via Autophagy and Senescence in NSCLC Cells

Abstract

The research has demonstrated a synergistic anticancer effect of Seabuckthorn pulp oil (SBO) and the standard chemotherapy regimen Docetaxel (DTX) against two non-small cell lung cancer (NSCLC) cell lines: A549 and H23. The synergizing effect of an SBO and DTX combination was detected utilizing SRB assay and combination index (CI) approaches. Flow cytometry was carried out using fluorescent probes to measure cell cycle analysis by DNA content and reactive oxygen species (ROS) generation. Further, we demonstrated that the synergistic anticancer activity of SBO merged with DTX was achieved by caspase-independent autophagy and senescence induction. These changes were concomitant with increased generation of ROS production and microtubule-associated protein 1 light chain 3 (LC3) protein expression, G1-phase arrest, and enhanced senescence-associated β-galactosidase staining activity. Our data also demonstrated that SBO or DTX treatment groups solely upregulated the phosphorylation of ERK, which coincided with the induction of autophagy vacuoles and was functionally associated with ROS activation. Moreover, endogenous LC3 puncta staining was performed and monitored by confocal microscopy. Overall, these results suggest new mechanisms for the antitumor activity of SBO co-treated with DTX through triggering autophagic cell death and senescence against cancer cells as a result of sustained ERK phosphorylation and intracellular ROS production in NSCLC. In addition, we also highlight SBO as an alternative therapeutic option or adjunct therapeutic strategy in combination with chemotherapeutic agents in lung cancer therapy management.