Modulation in the activity of lactate dehydrogenase and level of c-Myc and c-Fos by modified base queuine in cancer.
Cancer is characterized by uncontrolled cell growth, which results from unlimited proliferation and disturbs various cellular activities. Queuine is a highly modified base analogue of guanine found at first anti-codon position of specific tRNAs i.e. tRNA(Tyr), tRNA(His), tRNA(Asp) and tRNA(Asn). These tRNAs are known as Q-family of tRNA. The tRNAs of Q-family are completely modified to Q-tRNAs in terminally differentiated somatic cells, however hypomodification of Q-tRNA is closely associated with cell proliferation and malignancy. Queuosine modification of tRNAs may be essential for normal development, differentiation and cellular functions. Physiological role of queuine remains ill defined but direct or indirect evidences suggest that queuine or Q-tRNA participates in many cellular functions such as regulation of cell proliferation, control of glycolytic metabolism, alteration in expression of proto-oncogenes, modulation of signal transduction pathways but the mechanism is not well known. Increase in LDH-A expression regulated by c-myc is well documented in a variety of tumor cells. Overexpression of proto-oncogenes cause deregulated cellular responses which may lead to development of cancer. The cellular proto-oncogenes like c-myc and c-fos have important role in cell growth, proliferation and differentiation. The present study is aimed to investigate queuine mediated modulation in the activity of lactate dehydrogenase and expression of proto-oncogenes like c-myc and c-fos in T-cell lymphoma (DLAT) induced cancerous mouse. The results indicate that elevated lactate dehydrogenase activity is brought down by queuine treatments and the elevated levels of c-Myc and c-Fos in DLAT cancerous mouse are down-regulated, suggesting that queuine inhibits anaerobic metabolism and cell proliferation.
Pathak
Chandramani
C
Biochemistry & Molecular Biology Laboratory, Center of Advanced Study in Zoology, Banaras Hindu University, Varanasi, India.
Jaiswal
Yogesh K
YK
Vinayak
Manjula
M
D000818:Animals; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*
D007527:Isoenzymes; C489427:MYC protein, human; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D006147:Guanine; C019549:queuine; D007770:L-Lactate Dehydrogenase