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Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice.

Mishra S, Vinayak M - BMC Complement Altern Med (2015)

Bottom Line: Activation of different PKC isozymes results in distinct cellular responses.The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes.The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India.

ABSTRACT

Background: Protein kinase C regulates various cellular processes including cell proliferation, cell adhesion, apoptosis, angiogenesis, invasion, and metastasis. Activation of different PKC isozymes results in distinct cellular responses. Novel PKCs are mainly involved in apoptotic process. Atypical PKC subfamily plays a critical role in cell proliferation and apoptosis, cell differentiation and motility. However, Atypical PKCs show contradictory regulation in different tissues or cancer cells. The mechanism of diversified effects is not well explored. Antioxidant ellagic acid shows hepatoprotective, anti-carcinogenic and anti-mutagenic properties. Present study is focused to analyze the effect of ellagic acid on novel and atypical isozymes of PKC in regulation of PKC-mediated apoptosis in liver of lymphoma bearing mice. Implication of ellagic acid treatment to DL mice was analyzed on caspase-3 mediated apoptosis via PKCδ induced activation; and on maintenance of adequate supply of energy during cancer growth.

Methods: 15-20 weeks old adult DL mice were divided into four groups (n=6). Group 2, 3, 4 were treated with different doses of ellagic acid (40 mg/kg, 60 mg/kg and 80 mg/kg bw). The mice were sacrificed after 19 days of treatment and liver was used for study. The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes. Apoptotic potentiality of ellagic acid was checked on activities of caspase-3 and PKCδ in terms of their catalytic fragments. Aerobic glycolysis was monitored by LDH activity, especially activity of LDH A.

Results: Ellagic acid treatment caused up regulation of expression of almost all novel and atypical PKC isozymes. Activities of PKCδ and caspase-3 were enhanced by ellagic acid, however activities of total LDH and LDH-A were inhibited.

Conclusion: The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.

No MeSH data available.


Related in: MedlinePlus

Effect of ellagic acid on activity and expression of LDH- A. a In gel assay showing LDH-A activity. b RT-PCR analysis showing mRNA expression of LDH-A. Values are expressed as mean ± SD, * indicates that groups differ significantly from DL at the level of significance p < 0.05 using one way ANOVA followed by Tukey test. N, DL, DLT40, DLT60 and DLT80 represents normal, Dalton’s lymphoma bearing, and Dalton’s lymphoma bearing mice treated with 40, 60, 80 mg/kg body weight of ellagic acid respectively
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Fig7: Effect of ellagic acid on activity and expression of LDH- A. a In gel assay showing LDH-A activity. b RT-PCR analysis showing mRNA expression of LDH-A. Values are expressed as mean ± SD, * indicates that groups differ significantly from DL at the level of significance p < 0.05 using one way ANOVA followed by Tukey test. N, DL, DLT40, DLT60 and DLT80 represents normal, Dalton’s lymphoma bearing, and Dalton’s lymphoma bearing mice treated with 40, 60, 80 mg/kg body weight of ellagic acid respectively

Mentions: Glycolytic metabolism was monitored in terms of total activity of LDH as well as activity of anaerobic isozymes LDH-A. Total activity of LDH was analyzed by spectrophotometric assay, which was found to be approximately 3 fold higher in DL mice liver as compared to normal. The dose of 60 and 80 mg ellagic acid was found to decrease the activity approximately by half (Fig. 6). Activity of LDH-A measured by activity gel assay, was approximately double in DL mice liver as compared to normal and dose of 80 mg ellagic acid significantly inhibited the activity (Fig. 7a). Following the similar variation pattern, the expression of LDH-A in liver of DL mice was also elevated up to about double as compared to normal and ellagic acid treatment down regulated the expression significantly in a dose dependent manner (Fig. 7b).Fig. 6


Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice.

Mishra S, Vinayak M - BMC Complement Altern Med (2015)

Effect of ellagic acid on activity and expression of LDH- A. a In gel assay showing LDH-A activity. b RT-PCR analysis showing mRNA expression of LDH-A. Values are expressed as mean ± SD, * indicates that groups differ significantly from DL at the level of significance p < 0.05 using one way ANOVA followed by Tukey test. N, DL, DLT40, DLT60 and DLT80 represents normal, Dalton’s lymphoma bearing, and Dalton’s lymphoma bearing mice treated with 40, 60, 80 mg/kg body weight of ellagic acid respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536603&req=5

Fig7: Effect of ellagic acid on activity and expression of LDH- A. a In gel assay showing LDH-A activity. b RT-PCR analysis showing mRNA expression of LDH-A. Values are expressed as mean ± SD, * indicates that groups differ significantly from DL at the level of significance p < 0.05 using one way ANOVA followed by Tukey test. N, DL, DLT40, DLT60 and DLT80 represents normal, Dalton’s lymphoma bearing, and Dalton’s lymphoma bearing mice treated with 40, 60, 80 mg/kg body weight of ellagic acid respectively
Mentions: Glycolytic metabolism was monitored in terms of total activity of LDH as well as activity of anaerobic isozymes LDH-A. Total activity of LDH was analyzed by spectrophotometric assay, which was found to be approximately 3 fold higher in DL mice liver as compared to normal. The dose of 60 and 80 mg ellagic acid was found to decrease the activity approximately by half (Fig. 6). Activity of LDH-A measured by activity gel assay, was approximately double in DL mice liver as compared to normal and dose of 80 mg ellagic acid significantly inhibited the activity (Fig. 7a). Following the similar variation pattern, the expression of LDH-A in liver of DL mice was also elevated up to about double as compared to normal and ellagic acid treatment down regulated the expression significantly in a dose dependent manner (Fig. 7b).Fig. 6

Bottom Line: Activation of different PKC isozymes results in distinct cellular responses.The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes.The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India.

ABSTRACT

Background: Protein kinase C regulates various cellular processes including cell proliferation, cell adhesion, apoptosis, angiogenesis, invasion, and metastasis. Activation of different PKC isozymes results in distinct cellular responses. Novel PKCs are mainly involved in apoptotic process. Atypical PKC subfamily plays a critical role in cell proliferation and apoptosis, cell differentiation and motility. However, Atypical PKCs show contradictory regulation in different tissues or cancer cells. The mechanism of diversified effects is not well explored. Antioxidant ellagic acid shows hepatoprotective, anti-carcinogenic and anti-mutagenic properties. Present study is focused to analyze the effect of ellagic acid on novel and atypical isozymes of PKC in regulation of PKC-mediated apoptosis in liver of lymphoma bearing mice. Implication of ellagic acid treatment to DL mice was analyzed on caspase-3 mediated apoptosis via PKCδ induced activation; and on maintenance of adequate supply of energy during cancer growth.

Methods: 15-20 weeks old adult DL mice were divided into four groups (n=6). Group 2, 3, 4 were treated with different doses of ellagic acid (40 mg/kg, 60 mg/kg and 80 mg/kg bw). The mice were sacrificed after 19 days of treatment and liver was used for study. The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes. Apoptotic potentiality of ellagic acid was checked on activities of caspase-3 and PKCδ in terms of their catalytic fragments. Aerobic glycolysis was monitored by LDH activity, especially activity of LDH A.

Results: Ellagic acid treatment caused up regulation of expression of almost all novel and atypical PKC isozymes. Activities of PKCδ and caspase-3 were enhanced by ellagic acid, however activities of total LDH and LDH-A were inhibited.

Conclusion: The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.

No MeSH data available.


Related in: MedlinePlus