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

Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H - J. Exp. Clin. Cancer Res. (2010)

Bottom Line: TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Feist-Weiller Cancer Center, Louisiana State University, Shreveport, LA 71130 USA. sjafri@lsuhsc.edu

ABSTRACT

Background: Thymoquinone (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).

Methods: For 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-kappaB expression by TQ was determined using transgenic mice expressing a luciferase reporter.

Results: TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis. TQ at 100 microM and CDDP at 5 muM 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-kappaB expression which may explain its various cellular activities and this activity may prove useful in overcoming CDDP resistance from over expression of NF-kappaB.

Conclusions: Thus TQ and CDDP appear to be an active therapeutic combination in lung cancer.

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Related in: MedlinePlus

Effect of TQ on release of various cytokines was determined using RayBio Human Cytokines Antibody Array C Series 2000. TQ treated cell media was applied to cytokine membranes which were then exposed to a photographic film for 30 minutes and developed in a dark room. The three membranes represent various cytokines whose presence can be detected using this technique. Dots represent presence or absence of various cytokines which were then quantitated using image J Software expressed as mean integrated density.
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Figure 7: Effect of TQ on release of various cytokines was determined using RayBio Human Cytokines Antibody Array C Series 2000. TQ treated cell media was applied to cytokine membranes which were then exposed to a photographic film for 30 minutes and developed in a dark room. The three membranes represent various cytokines whose presence can be detected using this technique. Dots represent presence or absence of various cytokines which were then quantitated using image J Software expressed as mean integrated density.

Mentions: To assess the effect of TQ on release of various cytokines we assayed the culture media to determine if TQ affected expression of cytokines in NCI-H460 cell line. Of the panel of various cytokines measured using RayBio Human Cytokine Antibody Array C Series 2000, two cytokines ENA-78 and Gro-alpha were significantly lower in the media of cells exposed to 100 μM TQ as compared to control. The mean integrated density as measured by Image J Software for ENA-78 in the control treated group was 7083 as compared to 1732 in the TQ treated group and for Gro-alpha in the control group mean integrated density was 9970 as compared to 1877 in the TQ treated group (See figure 7-8)


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

Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H - J. Exp. Clin. Cancer Res. (2010)

Effect of TQ on release of various cytokines was determined using RayBio Human Cytokines Antibody Array C Series 2000. TQ treated cell media was applied to cytokine membranes which were then exposed to a photographic film for 30 minutes and developed in a dark room. The three membranes represent various cytokines whose presence can be detected using this technique. Dots represent presence or absence of various cytokines which were then quantitated using image J Software expressed as mean integrated density.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2909169&req=5

Figure 7: Effect of TQ on release of various cytokines was determined using RayBio Human Cytokines Antibody Array C Series 2000. TQ treated cell media was applied to cytokine membranes which were then exposed to a photographic film for 30 minutes and developed in a dark room. The three membranes represent various cytokines whose presence can be detected using this technique. Dots represent presence or absence of various cytokines which were then quantitated using image J Software expressed as mean integrated density.
Mentions: To assess the effect of TQ on release of various cytokines we assayed the culture media to determine if TQ affected expression of cytokines in NCI-H460 cell line. Of the panel of various cytokines measured using RayBio Human Cytokine Antibody Array C Series 2000, two cytokines ENA-78 and Gro-alpha were significantly lower in the media of cells exposed to 100 μM TQ as compared to control. The mean integrated density as measured by Image J Software for ENA-78 in the control treated group was 7083 as compared to 1732 in the TQ treated group and for Gro-alpha in the control group mean integrated density was 9970 as compared to 1877 in the TQ treated group (See figure 7-8)

Bottom Line: TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Feist-Weiller Cancer Center, Louisiana State University, Shreveport, LA 71130 USA. sjafri@lsuhsc.edu

ABSTRACT

Background: Thymoquinone (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).

Methods: For 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-kappaB expression by TQ was determined using transgenic mice expressing a luciferase reporter.

Results: TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis. TQ at 100 microM and CDDP at 5 muM 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-kappaB expression which may explain its various cellular activities and this activity may prove useful in overcoming CDDP resistance from over expression of NF-kappaB.

Conclusions: Thus TQ and CDDP appear to be an active therapeutic combination in lung cancer.

Show MeSH
Related in: MedlinePlus