Curcumin enhances the effects of TRAIL in TRAIL-resistant non-small cell lung cancer cell lines

TRAIL acts as a selective anticancer agent in non-small cell lung cancer (NSCLC). However, some NSCLC are resistance to TRAIL due to the presence of several anti-apoptotic mechanisms. With the help of natural compound such as curcumin, TRAIL-resistance can be overcome and the effect of TRAIL-induce apoptosis in NSCLC can be improved. In this study, we investigated the effect of curcumin in NSCLC as sensitiser to TRAIL as well as their molecular underlying mechanism.

Proliferation assay was conducted to determine whether curcumin could enhance the cytotoxic effect of TRAIL in NSCLC cell lines. Flow cytometry was performed for the assessment of TRAIL receptors expression (DR4 and DR5) and apoptosis assay (Annexin-V / PI staining). Gene expression analysis using RT² profiler PCR array and KEGG tools were performed to analyse the transcriptional levels of 84 significant apoptotic genes in NSCLC.

Treatment of NSCLC cell lines with TRAIL revealed that NSCLC cell lines can be classified as TRAIL-sensitive (H2170 and H1437) and TRAIL-resistant (A549 and H1299) based on their IC₅₀ values. H1299 has slightly lower expression of DR5, as compared to the other NSCLC cell lines which have more than 90% expression of DR4 and DR5. The combined treatment of curcumin and TRAIL were able to reduce cell viability and enhanced apoptosis in both TRAIL resistant and sensitive NSCLC cells than TRAIL alone. In addition, the combined treatment seems to induce the intrinsic apoptotic pathway in P53-deficient H1299, by activating the pro-apoptotic genes which are independent of P53.

Hence, this study provides evidence on the potential of curcumin as a sensitiser to enhance the efficacy of TRAIL in NSCLC and in TRAIL-resistance NSCLC.