title: Ellagic acid induces novel and atypical PKC isoforms and promotes caspase-3 dependent apoptosis by blocking energy metabolism.
abstract: Antioxidant ellagic acid is a herbal polyphenolic compound shown to possess growth-inhibiting and apoptotic activities in cancer. Protein kinase C (PKC) plays an important role in cell proliferation, apoptosis, and differentiation. Apoptosis of tumor cells is induced by inactivation of glycolytic enzyme of anaerobic metabolism, lactate dehydrogenase (LDH)-A, and by activating apoptotic protein caspase-3 via PKCδ. The present study aims to analyze the role of ellagic acid on regulation of novel and atypical isozymes of PKC to modulate apoptosis and anaerobic metabolism to prevent lymphoma growth as its role on classical PKCs is reported earlier. Expression of novel and atypical isozymes of PKC, activity of PKCδ, expression and activity of caspase-3, and LDH-A have been analyzed. Expression is measured by RT-PCR, activities of PKCδ as level of its catalytic fragment, caspase-3 as level of its p17 fragment, and LDH-A by specific staining. Lymphoma bearing mice were treated with 3 different doses of ellagic acid. The treatment enhanced expression of all novel and atypical PKCs, activity and expression of caspase-3, and activity of PKCδ but decreased activity and expression of LDH-A. Our results suggest that ellagic acid induces apoptosis via novel and atypical PKCs in association with caspase-3 and induces cancer cell death by blocking the energy metabolism.
authors.affiliation: a Biochemistry & Molecular Biology Unit , Centre of Advanced Study in Zoology, Banaras Hindu University , Varanasi , India.
authors.forename: Sudha
authors.initials: S
authors.lastname: Mishra
authors.forename: Manjula
authors.initials: M
authors.lastname: Vinayak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004610:Ellagic Acid / Q000494:pharmacology*; D004734:Energy Metabolism; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D064209:Phytochemicals; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D007527:Isoenzymes; D064209:Phytochemicals; D004610:Ellagic Acid; D007770:L-Lactate Dehydrogenase; C115015:PKC-3 protein; D011493:Protein Kinase C; C505409:Casp3 protein, mouse; D053148:Caspase 3