title: Quercetin regresses Dalton's lymphoma growth via suppression of PI3K/AKT signaling leading to upregulation of p53 and decrease in energy metabolism.
abstract: Various oncogenes are associated with deregulation in cell proliferation, apoptosis, and cell survival, which ultimately cause cancerous growth. Phosphatidylinositol 3-kinase (PI3K) mediated signaling plays a key role in malignant transformation. Cell proliferation and cell survival of tumor cell are induced by hyper activation of PI3K, AKT1, glycolytic enzyme LDH-A, and inactivation of tumor suppressor gene p53. Dietary flavonoids such as quercetin are considered a powerful modulator of different cellular signaling pathways. The present study is focused on the role of quercetin on regulation of PI3K/AKT pathways in Dalton's lymphoma mice. Effect of quercetin was analyzed in ascite cells in terms of cell viability, glycolytic metabolism as well as expression, and level of PI3K (regulatory and catalytic subunit), AKT1, and p53 using standard methods. Results reflect hyperactivation of PI3K signaling in ascite cells of Dalton's lymphoma mice, leading to activation of AKT1 and inactivation of p53. Quercetin modulates the pathway toward suppression of lymphoma. Glycolytic metabolism was also downregulated by quercetin. Its tumor suppressor activity was confirmed by morphological parameters and longevity of mice. The findings suggest that quercetin may contribute to lymphoma prevention by downregulating PI3K-AKT1-p53 pathway as well as by glycolytic metabolism.
authors: a Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology , Banaras Hindu University , Varanasi , India.
authors: Akhilendra Kumar
authors: AK
authors: Maurya
authors: Manjula
authors: M
authors: Vinayak
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D000080864:Lactate Dehydrogenase 5; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D058539:Phosphatidylinositol 3-Kinase / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt