The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: in vitro and in vivo investigations

Abstract

Abstract Background: Malignant and aggressive, small cell lung cancer (SCLC) comprises about 15% of all diagnosed lung cancer cases. With primary therapeutic options like chemotherapy accompanied by enfeebling side-effects, interest has been soaring in the therapeutic competencies of herbs. One such herb is Nigella sativa. Surviving millennia, originating, and populating Middle-eastern and Mediterranean culture and cuisine, Nigella sativa has been investigated for its anti-cancer effects. The pharmacological driving force behind beneficial properties of Nigella sativa is the quinone, thymoquinone (TQ). Much research has been done on anti-cancer effects of TQ in different cancers. However, for its effects in SCLC, a lone paper exists in the entire NCBI database. This necessitates more and detailed investigations. Methods: The current study examines impacts of TQ in vitro on 5 SCLC cell lines and in vivo in a nude mice xenograft model. The in vitro effects of TQ on SCLC (a) cell viability were determined through MTT assay and crystal violet assay; (b) apoptosis were measured via apoptosis marker phosphatidyl serine externalization through the annexin-V assay and mitochondrial membrane depolarization through the JC-1 assay; (c) cell cycle arrest via PI staining; (d) intracellular ROS levels through H2DCFDA staining, and protein expression in concomitant signaling pathways through western blotting. As for the in vivo effects of TQ on SCLC, (a) tumor weight and volume were determined, (b) selected protein expression in selected concomitant signaling pathways through western blotting. Results: TQ effectuated reduction in cell viability, induction of apoptosis and S-phase arrest, depletion of reactive oxygen species, and alteration of protein expressions in associated signaling pathways. Furthermore, TQ exhibited tumor suppressive effect in a H446 SCLC xenograft model. Conclusions: Cytotoxic impacts of TQ stemming from anti-cancer mechanisms have been elucidated. The positive results obtained in this study warrant consequential future research.