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


CONCLUSIONS
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.
Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India.
Sudha
S
Mishra
Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India. manjulavinayak@rediffmail.com.
Manjula
M
Vinayak
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004610:Ellagic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D000975:Antioxidants; D020536:Enzyme Activators; D007527:Isoenzymes; D010936:Plant Extracts; D004610:Ellagic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D011493:Protein Kinase C; D053148:Caspase 3