Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo

Abstract

BackgroundThymoquinone (TQ) is a compound extracted from Black Caraway seeds of Nigella Sativa and is active against various cancers. Cisplatin (CDDP) is the most active chemotherapeutic agent in Lung Cancer. Here we report activity of TQ against non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines alone and in combination with Cisplatin (CDDP).MethodsFor proliferation MTT assay, cell viability trypan blue assay and for apoptosis Annexin-V FITC assay were used in NCI-H460 and NCI-H146 cell lines. Inhibition of invasion by TQ was assessed using Matrigel assay and its affect on release of various cytokines was determined using RayBio Human Cytokine detection kit. Mouse xenograft model using NCI-H460 was used to determine in vivo activity of TQ and CDDP. Inhibition of LPS induced NF-κB expression by TQ was determined using transgenic mice expressing a luciferase reporter.ResultsTQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis. TQ at 100 μM and CDDP at 5 μM inhibited cell proliferation by nearly 90% and the combination showed synergism. TQ was able to induced apoptosis in both NCI-H460 and NCI-H146 cell lines. TQ also appears to affect the extracellular environment inhibiting invasion and reducing the production of two cytokines ENA-78 and Gro-alpha which are involved in neo-angiogenesis. Using a mouse xenograft model we were able to demonstrate that combination of TQ and CDDP was well tolerated and significantly reduced tumor volume and tumor weight without additional toxicity to the mice. In the combination arms (TQ5 mg/kg/Cis 2.5 mg/kg) tumor volume was reduced by 59% and (TQ20 mg/kg/Cis 2.5 mg/kg) by 79% as compared to control which is consistent with in vitro data. TQ down regulated NF-κB expression which may explain its various cellular activities and this activity may prove useful in overcoming CDDP resistance from over expression of NF-κB.ConclusionsThus TQ and CDDP appear to be an active therapeutic combination in lung cancer.

Effect of thymoquinone on head and neck squamous cell carcinoma cells in vitro: Synergism with radiation

“…This was demonstrated with proliferation assays in two HNSCC cell lines. These results differ from previous findings (14,16). Jafri et al (16) combined TQ with cisplatin in lung cancer cell lines (NCI-H460 and NCI-H146) in vitro and in a mouse xenograft model using NCI-H460 in vivo.…”

“…These results differ from previous findings (14,16). Jafri et al (16) combined TQ with cisplatin in lung cancer cell lines (NCI-H460 and NCI-H146) in vitro and in a mouse xenograft model using NCI-H460 in vivo. The study described a synergistic effect of the combination treatment and concluded that TQ and cisplatin appear to be an active therapeutic combination in lung cancer.…”

Cytotoxicity of Nigella Sativa Seed Oil and Extract Against Human Lung Cancer Cell Line

“…Recent studies indicate that N sativa extracts has cytotoxic effects against different types of cancer cell lines in vitro (Jafri et al, 2010;Bourgou et al, 2012;VSPK et al, 2013). Therefore, the present study was undertaken to provide comparative data on the in vitro cytotoxic activity of different extracts of N sativa seeds against A-549, a human lung cancer cell lines.…”

Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

“…It tends to metastasize outside the chest two-thirds of the time at clinical presentation, and approximately only 7% of patients are alive for 5 years since the beginning of treatment [20]. Recently, new agents such as erlotinib and bevacizuman, have been approved for the treatment of lung cancer, however the 5-year survival rate reaching 16% still remains the same [6]. On the contrary to other agents targeting single gene product, epigenetic drugs have chromatin as their target through the inhibition of histone deacetylases (HDAC'S) and DNA methyltransferases (DNMT'S) therefore, they may act upon most or all tumor types [4].…”