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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 cordycepin + paclitaxel and/or cisplatin on cell cycle progression in MA-10 cells.Notes: The histogram plot of flow cytometry analysis in MA-10 cells treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 24 hours is illustrated in (A) (subG1, cells with less than normal amount of DNA content; G1/S, cells in G1 cell cycle phase; and G2/M, cell in G2/M cell cycle phase). The arrows indicate the increase in subG1 phase cells. Percentages of subG1 (B), G1/S (C), and G2/M (D) phase cell numbers are shown. *Indicates a statistically significant difference when compared with control (P<0.05).Abbreviations: Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide; T, paclitaxel.
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f2-ott-8-2345: Effects of cordycepin + paclitaxel and/or cisplatin on cell cycle progression in MA-10 cells.Notes: The histogram plot of flow cytometry analysis in MA-10 cells treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 24 hours is illustrated in (A) (subG1, cells with less than normal amount of DNA content; G1/S, cells in G1 cell cycle phase; and G2/M, cell in G2/M cell cycle phase). The arrows indicate the increase in subG1 phase cells. Percentages of subG1 (B), G1/S (C), and G2/M (D) phase cell numbers are shown. *Indicates a statistically significant difference when compared with control (P<0.05).Abbreviations: Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide; T, paclitaxel.

Mentions: To investigate whether cordycepin combined with paclitaxel and/or cisplatin could induce apoptosis, MA-10 cells were examined for DNA content by propidium iodide staining and flow cytometry analysis. A feature of cell apoptosis is DNA fragmentation of genomic DNA into multiples of 180–200 bp units. In the absence of drugs, cells can be divided into two phases, ie, the G1 (diploid) phase and G2/M phase, with greater numbers of cell accumulation in G1 phase than G2/M phase. In the presence of 100 μM cordycepin, 50 nM paclitaxel, but not cisplatin, and all the combination treatments for 24 hours, the percentage of abnormal DNA content in subG1 phase (haploid), increased (Figure 2A). Figure 2B demonstrates that the percentage of control cells in subG1 phase was approximately 5% and was increased significantly to 53.76% by cordycepin, 19.65% by paclitaxel, 53.53% by cisplatin + cordycepin, 18.34% by cisplatin + paclitaxel, 53.43% by cordycepin + paclitaxel, and 57.79% by cordycepin + cisplatin + paclitaxel after treatment for 24 hours (P<0.05). There was no difference between the control and cisplatin groups (Figure 2B). Figure 2C demonstrated that the percentage of control cells in G1 phase was approximately 70%, and was decreased significantly to 32.86% by cordycepin, 60.15% by paclitaxel, 58.76% by cisplatin, 30.2% by cisplatin + cordycepin, 37.12% by cisplatin + paclitaxel, 33.17% by cordycepin + paclitaxel, and 31.83% by cordycepin + cisplatin + paclitaxel after treatment for 24 hours (P<0.05). Figure 2D demonstrates that the percentage of control cells in G2/M phase was approximately 20%, which was increased significantly to 34.73% by cisplatin and 44.57% by cisplatin + paclitaxel after treatment for 24 hours (P<0.05). These results demonstrate that cordycepin combined with paclitaxel and/or cisplatin could induce apoptosis in 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 cordycepin + paclitaxel and/or cisplatin on cell cycle progression in MA-10 cells.Notes: The histogram plot of flow cytometry analysis in MA-10 cells treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 24 hours is illustrated in (A) (subG1, cells with less than normal amount of DNA content; G1/S, cells in G1 cell cycle phase; and G2/M, cell in G2/M cell cycle phase). The arrows indicate the increase in subG1 phase cells. Percentages of subG1 (B), G1/S (C), and G2/M (D) phase cell numbers are shown. *Indicates a statistically significant difference when compared with control (P<0.05).Abbreviations: Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide; T, paclitaxel.
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f2-ott-8-2345: Effects of cordycepin + paclitaxel and/or cisplatin on cell cycle progression in MA-10 cells.Notes: The histogram plot of flow cytometry analysis in MA-10 cells treated without or with 50 nM paclitaxel and/or 100 μM cisplatin +100 μM cordycepin for 24 hours is illustrated in (A) (subG1, cells with less than normal amount of DNA content; G1/S, cells in G1 cell cycle phase; and G2/M, cell in G2/M cell cycle phase). The arrows indicate the increase in subG1 phase cells. Percentages of subG1 (B), G1/S (C), and G2/M (D) phase cell numbers are shown. *Indicates a statistically significant difference when compared with control (P<0.05).Abbreviations: Cor, cordycepin; Cis, cisplatin; DMSO, dimethyl sulfoxide; T, paclitaxel.
Mentions: To investigate whether cordycepin combined with paclitaxel and/or cisplatin could induce apoptosis, MA-10 cells were examined for DNA content by propidium iodide staining and flow cytometry analysis. A feature of cell apoptosis is DNA fragmentation of genomic DNA into multiples of 180–200 bp units. In the absence of drugs, cells can be divided into two phases, ie, the G1 (diploid) phase and G2/M phase, with greater numbers of cell accumulation in G1 phase than G2/M phase. In the presence of 100 μM cordycepin, 50 nM paclitaxel, but not cisplatin, and all the combination treatments for 24 hours, the percentage of abnormal DNA content in subG1 phase (haploid), increased (Figure 2A). Figure 2B demonstrates that the percentage of control cells in subG1 phase was approximately 5% and was increased significantly to 53.76% by cordycepin, 19.65% by paclitaxel, 53.53% by cisplatin + cordycepin, 18.34% by cisplatin + paclitaxel, 53.43% by cordycepin + paclitaxel, and 57.79% by cordycepin + cisplatin + paclitaxel after treatment for 24 hours (P<0.05). There was no difference between the control and cisplatin groups (Figure 2B). Figure 2C demonstrated that the percentage of control cells in G1 phase was approximately 70%, and was decreased significantly to 32.86% by cordycepin, 60.15% by paclitaxel, 58.76% by cisplatin, 30.2% by cisplatin + cordycepin, 37.12% by cisplatin + paclitaxel, 33.17% by cordycepin + paclitaxel, and 31.83% by cordycepin + cisplatin + paclitaxel after treatment for 24 hours (P<0.05). Figure 2D demonstrates that the percentage of control cells in G2/M phase was approximately 20%, which was increased significantly to 34.73% by cisplatin and 44.57% by cisplatin + paclitaxel after treatment for 24 hours (P<0.05). These results demonstrate that cordycepin combined with paclitaxel and/or cisplatin could induce apoptosis in 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