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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

Flowcytometry data showing apoptosis in both NSCLC (NCI-H460) and SCLC (NCI-H146) cell lines 24 hrs after treatment with TQ 100 μM. 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V 24 hrs after treatment with TQ. Upper row represent NCI-H460 cells and Lower row NCI-H146. Left column represents control treated and the right column represents TQ treated.
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Figure 6: Flowcytometry data showing apoptosis in both NSCLC (NCI-H460) and SCLC (NCI-H146) cell lines 24 hrs after treatment with TQ 100 μM. 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V 24 hrs after treatment with TQ. Upper row represent NCI-H460 cells and Lower row NCI-H146. Left column represents control treated and the right column represents TQ treated.

Mentions: To determine if the decrease in proliferation and viability were a result of TQ induced apoptosis in the two cell lines, cells were assayed by Annexin V staining after exposure to TQ. After 24 hours treatment with 100 μM TQ about 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V compared to 2.0% and 34.5% Annexin V positive cells in the DMSO treated cell (Figure 6)


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)

Flowcytometry data showing apoptosis in both NSCLC (NCI-H460) and SCLC (NCI-H146) cell lines 24 hrs after treatment with TQ 100 μM. 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V 24 hrs after treatment with TQ. Upper row represent NCI-H460 cells and Lower row NCI-H146. Left column represents control treated and the right column represents TQ treated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Flowcytometry data showing apoptosis in both NSCLC (NCI-H460) and SCLC (NCI-H146) cell lines 24 hrs after treatment with TQ 100 μM. 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V 24 hrs after treatment with TQ. Upper row represent NCI-H460 cells and Lower row NCI-H146. Left column represents control treated and the right column represents TQ treated.
Mentions: To determine if the decrease in proliferation and viability were a result of TQ induced apoptosis in the two cell lines, cells were assayed by Annexin V staining after exposure to TQ. After 24 hours treatment with 100 μM TQ about 87.59% of NCI-H460 cells and 88.1% of NCI-H146 cells were positive for Annexin-V compared to 2.0% and 34.5% Annexin V positive cells in the DMSO treated cell (Figure 6)

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