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Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells.

Rombo R, Weiher H, Schmidt-Wolf IG - Ger Med Sci (2016)

Bottom Line: The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells.Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin.Abstract available from the publisher.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Oncology (CIO), University of Bonn, Bonn, Germany; Hochschule Bonn-Rhein-Sieg, Rheinbach, Germany.

ABSTRACT
We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

No MeSH data available.


Related in: MedlinePlus

Cytotoxic effects of chaetocin on cell viability of ccRCC cell lines A-498 (A) and CAKI-2 (B). Both cell lines were incubated in medium containing 0–400 nM chaetocin and the cell viability was determined after 1 day (red) and after 4 days (blue) by the use of the MTT assay. Triplicates were used for each sample to determine the mean ±SD. The significance was determined by the use of t-test (*=0.05–0.04, **=0.02–0.03, ***=<0.002). Cells without chaetocin treatment were used as negative control while cells treated with a deadly dose of DMSO were used as positive control.
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Figure 2: Cytotoxic effects of chaetocin on cell viability of ccRCC cell lines A-498 (A) and CAKI-2 (B). Both cell lines were incubated in medium containing 0–400 nM chaetocin and the cell viability was determined after 1 day (red) and after 4 days (blue) by the use of the MTT assay. Triplicates were used for each sample to determine the mean ±SD. The significance was determined by the use of t-test (*=0.05–0.04, **=0.02–0.03, ***=<0.002). Cells without chaetocin treatment were used as negative control while cells treated with a deadly dose of DMSO were used as positive control.

Mentions: Since the chosen chaetocin concentrations showed a weaker effect upon the viability of the ccRCC cell lines than expected, higher concentration in the range from 0–400 nM were chosen for the next chaetocin tittering. The cell viability was determined after 1 day and 4 days of incubation, without additional administration of chaetocin, in order to see if the cytotoxic effect of the medical agent increases or if the cells are able to regenerate (see Figure 2 (Fig. 2)). Figure 2A (Fig. 2) shows the results of the chaetocin titering with A-498 cells. The cell viability of the A-498 cell line already dropped to 67% after one day of incubation with 10 nM chaetocin compared to A-498 cells grown in the absence of chaetocin. A further decrease of the cell viability is observed at a concentration of 50 nM where only 51% of the cells remain alive. No further signal of living cells was detected at concentration of 100 nM and above. The four day incubation of the cell line along with chaetocin showed quite different results. The cell viability stays above 90% until a concentration of 100 nm is reached which still resulted in a cell viability of 63% and 6% of the cells stayed alive even at a concentration of 200 nM chaetocin. Figure 2B (Fig. 2) displays the cell viability of the CAKI-2 tumor cell line during the chaetocin titering. The viability stays above 80% until a chaetocin concentration of 20 nM is reached resulting in a drop to 76% viability. Even at higher concentrations like 200 nM 55% of the CAKI cell line were still alive and 8% at 400 nM. After four days of incubation, the cell viability of the CAKI-2 cell line is above 90% until it drops to 81% at a concentration of 50 nM chaetocin. The results for the one day and four day incubation are quite similar for the concentration from 10 nM–50 nM but at 100 nM the viability of the four day incubated cells dropped to 55% and down to 20% at 200 nM.


Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells.

Rombo R, Weiher H, Schmidt-Wolf IG - Ger Med Sci (2016)

Cytotoxic effects of chaetocin on cell viability of ccRCC cell lines A-498 (A) and CAKI-2 (B). Both cell lines were incubated in medium containing 0–400 nM chaetocin and the cell viability was determined after 1 day (red) and after 4 days (blue) by the use of the MTT assay. Triplicates were used for each sample to determine the mean ±SD. The significance was determined by the use of t-test (*=0.05–0.04, **=0.02–0.03, ***=<0.002). Cells without chaetocin treatment were used as negative control while cells treated with a deadly dose of DMSO were used as positive control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836455&req=5

Figure 2: Cytotoxic effects of chaetocin on cell viability of ccRCC cell lines A-498 (A) and CAKI-2 (B). Both cell lines were incubated in medium containing 0–400 nM chaetocin and the cell viability was determined after 1 day (red) and after 4 days (blue) by the use of the MTT assay. Triplicates were used for each sample to determine the mean ±SD. The significance was determined by the use of t-test (*=0.05–0.04, **=0.02–0.03, ***=<0.002). Cells without chaetocin treatment were used as negative control while cells treated with a deadly dose of DMSO were used as positive control.
Mentions: Since the chosen chaetocin concentrations showed a weaker effect upon the viability of the ccRCC cell lines than expected, higher concentration in the range from 0–400 nM were chosen for the next chaetocin tittering. The cell viability was determined after 1 day and 4 days of incubation, without additional administration of chaetocin, in order to see if the cytotoxic effect of the medical agent increases or if the cells are able to regenerate (see Figure 2 (Fig. 2)). Figure 2A (Fig. 2) shows the results of the chaetocin titering with A-498 cells. The cell viability of the A-498 cell line already dropped to 67% after one day of incubation with 10 nM chaetocin compared to A-498 cells grown in the absence of chaetocin. A further decrease of the cell viability is observed at a concentration of 50 nM where only 51% of the cells remain alive. No further signal of living cells was detected at concentration of 100 nM and above. The four day incubation of the cell line along with chaetocin showed quite different results. The cell viability stays above 90% until a concentration of 100 nm is reached which still resulted in a cell viability of 63% and 6% of the cells stayed alive even at a concentration of 200 nM chaetocin. Figure 2B (Fig. 2) displays the cell viability of the CAKI-2 tumor cell line during the chaetocin titering. The viability stays above 80% until a chaetocin concentration of 20 nM is reached resulting in a drop to 76% viability. Even at higher concentrations like 200 nM 55% of the CAKI cell line were still alive and 8% at 400 nM. After four days of incubation, the cell viability of the CAKI-2 cell line is above 90% until it drops to 81% at a concentration of 50 nM chaetocin. The results for the one day and four day incubation are quite similar for the concentration from 10 nM–50 nM but at 100 nM the viability of the four day incubated cells dropped to 55% and down to 20% at 200 nM.

Bottom Line: The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells.Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin.Abstract available from the publisher.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Oncology (CIO), University of Bonn, Bonn, Germany; Hochschule Bonn-Rhein-Sieg, Rheinbach, Germany.

ABSTRACT
We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

No MeSH data available.


Related in: MedlinePlus