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Apoptotic effect of cordycepin combined with cisplatin and/or paclitaxel on MA-10 mouse Leydig tumor cells.

Kang FC, Chen PJ, Pan BS, Lai MS, Chen YC, Huang BM - Onco Targets Ther (2015)

Bottom Line: Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis.Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells.Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Chi Mei Medical Center, Chiali, Republic of China.

ABSTRACT

Background: Chemotherapy is not limited to a single treatment, and the evidence demonstrates that different drug combinations can have positive results in patients. In this study, we sought to determine whether cordycepin combined with cisplatin and/or paclitaxel would have an additive effective on inducing apoptosis in mouse Leydig tumor cells, and the mechanisms were also briefly examined.

Methods: The additive effects of cordycepin combined with cisplatin and/or paclitaxel on apoptosis in MA-10 cells were investigated by monitoring changes in morphological characteristics and examining cell viability, flow cytometry assays, and Western blot analyses.

Results: Combination of cordycepin plus cisplatin and/or paclitaxel for 12 and 24 hours induced apoptotic features in MA-10 cells. The MTT assay showed that the combination treatment reduced the viability of MA-10 cells in a dose-dependent manner, with additive effects. Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis. Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells.

Conclusion: Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways.

No MeSH data available.


Related in: MedlinePlus

Effects of paclitaxel and/or cisplatin + cordycepin on the protein expression of p53 in MA-10 cells.Notes: The cells were then treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 12 and 24 hours. After the treatments, the p-p53 (53 kDa) protein was detected by Western blot (A). The immunoblot represents the observations from one single experiment reported three times. The integrated optical density of p-p53 was analyzed after normalization with t-p53 (53 kDa) in each lane (B). Each datum point represents the mean ± standard error of the mean of three separate experiments. *Indicates that the means are significantly different compared with control (P<0.05).Abbreviations: p-, phosphorylated; t-, total; Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide.
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f8-ott-8-2345: Effects of paclitaxel and/or cisplatin + cordycepin on the protein expression of p53 in MA-10 cells.Notes: The cells were then treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 12 and 24 hours. After the treatments, the p-p53 (53 kDa) protein was detected by Western blot (A). The immunoblot represents the observations from one single experiment reported three times. The integrated optical density of p-p53 was analyzed after normalization with t-p53 (53 kDa) in each lane (B). Each datum point represents the mean ± standard error of the mean of three separate experiments. *Indicates that the means are significantly different compared with control (P<0.05).Abbreviations: p-, phosphorylated; t-, total; Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide.

Mentions: The tumor suppressor p53 is the central player in a network protecting higher eukaryotic cells against various types of damage that might lead to genetic alterations.33 In addition, p53 protein can functionally interact with MAPK pathways.34 Moreover, studies have demonstrated that p53 can be induced by two widely used anticancer agents, ie, cisplatin and paclitaxel.35 Hence, we investigated whether expression of p53 protein was involved in apoptosis of MA-10 cells activated by cordycepin + paclitaxel and/or cisplatin. Expression of phosphorylated p53 protein in MA-10 cells treated with control and DMSO was low (Figure 8A and B). After 12 hours of treatment, cordycepin alone and cisplatin + cordycepin induced significant expression of phosphorylated p53 (P<0.05, Figure 8B). After 24 hours of treatment, cordycepin, cisplatin + cordycepin, cordycepin + paclitaxel, and cordycepin + cisplatin + paclitaxel significantly induced expression of phosphorylated p53 in MA-10 cells (P<0.05, Figure 8B). These results indicate that cordycepin, but not paclitaxel or cisplatin, could activate the p53 pathway to induce apoptosis of MA-10 cells.


Apoptotic effect of cordycepin combined with cisplatin and/or paclitaxel on MA-10 mouse Leydig tumor cells.

Kang FC, Chen PJ, Pan BS, Lai MS, Chen YC, Huang BM - Onco Targets Ther (2015)

Effects of paclitaxel and/or cisplatin + cordycepin on the protein expression of p53 in MA-10 cells.Notes: The cells were then treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 12 and 24 hours. After the treatments, the p-p53 (53 kDa) protein was detected by Western blot (A). The immunoblot represents the observations from one single experiment reported three times. The integrated optical density of p-p53 was analyzed after normalization with t-p53 (53 kDa) in each lane (B). Each datum point represents the mean ± standard error of the mean of three separate experiments. *Indicates that the means are significantly different compared with control (P<0.05).Abbreviations: p-, phosphorylated; t-, total; Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4562734&req=5

f8-ott-8-2345: Effects of paclitaxel and/or cisplatin + cordycepin on the protein expression of p53 in MA-10 cells.Notes: The cells were then treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 12 and 24 hours. After the treatments, the p-p53 (53 kDa) protein was detected by Western blot (A). The immunoblot represents the observations from one single experiment reported three times. The integrated optical density of p-p53 was analyzed after normalization with t-p53 (53 kDa) in each lane (B). Each datum point represents the mean ± standard error of the mean of three separate experiments. *Indicates that the means are significantly different compared with control (P<0.05).Abbreviations: p-, phosphorylated; t-, total; Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide.
Mentions: The tumor suppressor p53 is the central player in a network protecting higher eukaryotic cells against various types of damage that might lead to genetic alterations.33 In addition, p53 protein can functionally interact with MAPK pathways.34 Moreover, studies have demonstrated that p53 can be induced by two widely used anticancer agents, ie, cisplatin and paclitaxel.35 Hence, we investigated whether expression of p53 protein was involved in apoptosis of MA-10 cells activated by cordycepin + paclitaxel and/or cisplatin. Expression of phosphorylated p53 protein in MA-10 cells treated with control and DMSO was low (Figure 8A and B). After 12 hours of treatment, cordycepin alone and cisplatin + cordycepin induced significant expression of phosphorylated p53 (P<0.05, Figure 8B). After 24 hours of treatment, cordycepin, cisplatin + cordycepin, cordycepin + paclitaxel, and cordycepin + cisplatin + paclitaxel significantly induced expression of phosphorylated p53 in MA-10 cells (P<0.05, Figure 8B). These results indicate that cordycepin, but not paclitaxel or cisplatin, could activate the p53 pathway to induce apoptosis of MA-10 cells.

Bottom Line: Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis.Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells.Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Chi Mei Medical Center, Chiali, Republic of China.

ABSTRACT

Background: Chemotherapy is not limited to a single treatment, and the evidence demonstrates that different drug combinations can have positive results in patients. In this study, we sought to determine whether cordycepin combined with cisplatin and/or paclitaxel would have an additive effective on inducing apoptosis in mouse Leydig tumor cells, and the mechanisms were also briefly examined.

Methods: The additive effects of cordycepin combined with cisplatin and/or paclitaxel on apoptosis in MA-10 cells were investigated by monitoring changes in morphological characteristics and examining cell viability, flow cytometry assays, and Western blot analyses.

Results: Combination of cordycepin plus cisplatin and/or paclitaxel for 12 and 24 hours induced apoptotic features in MA-10 cells. The MTT assay showed that the combination treatment reduced the viability of MA-10 cells in a dose-dependent manner, with additive effects. Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis. Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells.

Conclusion: Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways.

No MeSH data available.


Related in: MedlinePlus