Limits...
Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells.

van Haaften C, Boot A, Corver WE, van Eendenburg JD, Trimbos BJ, van Wezel T - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC.Additionally, synergistic drug combinations showed increased apoptosis.These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. carocell@planet.nl.

ABSTRACT

Background: Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed.

Methods: Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit.

Results: In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis.

Conclusions: Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

No MeSH data available.


Related in: MedlinePlus

Synergistic effects of combination treatment with EPD on ovarian cancer cell lines and normal fibroblasts. Relative viability is shown for each single compound. E: EPD, C: cisplatin, T: paclitaxel. Synergism was observed between EPD and paclitaxel for SK-OV-3 and JC, whereas for JC-pl the combination of EPD and cisplatin was found to be synergistic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4472250&req=5

Fig1: Synergistic effects of combination treatment with EPD on ovarian cancer cell lines and normal fibroblasts. Relative viability is shown for each single compound. E: EPD, C: cisplatin, T: paclitaxel. Synergism was observed between EPD and paclitaxel for SK-OV-3 and JC, whereas for JC-pl the combination of EPD and cisplatin was found to be synergistic.

Mentions: The relative cell viability of the four cell lines and normal fibroblasts, treated with EPD, cisplatin and paclitaxel are shown in Figure 1. Treatment with EPD, paclitaxel or cisplatin alone resulted in reduced viability in the cell lines, ranging between 41 and 93% of viable cells. Normal skin fibroblasts were affected mostly by paclitaxel after 72 hrs. The combination treatments of EPD with cisplatin and paclitaxel showed increased activity in the different cell lines. To evaluate whether these combination treatments were synergistic drug interactions, a simplified version of the Bliss independence model was applied [14]. When two drugs exert their effects independent to one another, the resulting relative viability after drug treatment is expected to equal the product of the relative viability after treatment with the individual drugs. When the observed viability is higher than the expected based on the individual drug effects, the compounds inhibit each others effects; antagonism. However, when observed viability after combination treatment is lower than the expected viability, then this is an indication of a synergistic drug interaction.Figure 1


Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells.

van Haaften C, Boot A, Corver WE, van Eendenburg JD, Trimbos BJ, van Wezel T - J. Exp. Clin. Cancer Res. (2015)

Synergistic effects of combination treatment with EPD on ovarian cancer cell lines and normal fibroblasts. Relative viability is shown for each single compound. E: EPD, C: cisplatin, T: paclitaxel. Synergism was observed between EPD and paclitaxel for SK-OV-3 and JC, whereas for JC-pl the combination of EPD and cisplatin was found to be synergistic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472250&req=5

Fig1: Synergistic effects of combination treatment with EPD on ovarian cancer cell lines and normal fibroblasts. Relative viability is shown for each single compound. E: EPD, C: cisplatin, T: paclitaxel. Synergism was observed between EPD and paclitaxel for SK-OV-3 and JC, whereas for JC-pl the combination of EPD and cisplatin was found to be synergistic.
Mentions: The relative cell viability of the four cell lines and normal fibroblasts, treated with EPD, cisplatin and paclitaxel are shown in Figure 1. Treatment with EPD, paclitaxel or cisplatin alone resulted in reduced viability in the cell lines, ranging between 41 and 93% of viable cells. Normal skin fibroblasts were affected mostly by paclitaxel after 72 hrs. The combination treatments of EPD with cisplatin and paclitaxel showed increased activity in the different cell lines. To evaluate whether these combination treatments were synergistic drug interactions, a simplified version of the Bliss independence model was applied [14]. When two drugs exert their effects independent to one another, the resulting relative viability after drug treatment is expected to equal the product of the relative viability after treatment with the individual drugs. When the observed viability is higher than the expected based on the individual drug effects, the compounds inhibit each others effects; antagonism. However, when observed viability after combination treatment is lower than the expected viability, then this is an indication of a synergistic drug interaction.Figure 1

Bottom Line: The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC.Additionally, synergistic drug combinations showed increased apoptosis.These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. carocell@planet.nl.

ABSTRACT

Background: Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed.

Methods: Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit.

Results: In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis.

Conclusions: Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

No MeSH data available.


Related in: MedlinePlus