Anticancer activity of thymoquinone in non-small cell lung cancer and possible involvement of PPAR-γ pathway.

Abstract

Purpose: Thymoquinone (TQ) is an ingredient of Nigella sativa and Cisplatin (CDDP) is the most active chemotherapeutic agent in lung cancer. The objective of this study was to assess the anticancer effects of TQ in non-small cell lung cancer (NSCLC) cells, and its effect on the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway.

Methods: Annexin-V FITC assay was used in the NCI-H460 cell line for apoptosis. The mRNA expression of PPAR-γ, P53, BCL-2, Retinoblastoma (Rb), Cyclin-D1, RELA, Tumor necrosis Factor alpha and in a dose-dependent manner TQ activated caspases 9, 8, 7, and 3 were examined using quantitative real-time reverse transcriptase polymerase chain reaction.

Results: PPAR-γ protein levels elevated in all treatment groups, especially in the CDDP + TQ group as observed in mRNA results. In the CDDP + TQ + IR group, the reduction of NF-κB pathway, which provides survival and growth signaling, confirms the potential of this treatment in lung cancer treatment approach similar to p53, Rb, and PPAR-γ results. When the effect of treatment on the viability of NSCLC cells was assessed with flow cytometry analyzes, TQ alone supported death compared to control, cell viability also decreased in the CDDP or IR groups to which TQ was added.

Conclusion: As a result, combined therapy of TQ, CDDP, and IR have been shown to increase apoptosis by sensitizing NSCLC cells to IR. These in vitro results are the basis because they demonstrate that it may be useful to include TQ in combined NSCLC cell treatments to reduce tumor progression.