Possible involvement of queuine in regulation of cell proliferation

Abstract

An increase in cell number is one of the most prominent characteristics of cancer cells. This may be caused by an increase in cell proliferation or decrease in cell death. Queuine is one of the modified base which is found at first anticodon position of specific tRNAs. It is ubiquitously present throughout the living system except mycoplasma and yeast. 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. Queuine participates at various cellular functions such as regulation of cell proliferation, cell signaling and alteration in the expression of growth associated proto-oncogenes. Like other proto-oncogenes bcl2 is known to involve in cell survival by inhibiting apoptosis. Queuine or Q-tRNA is suggested to inhibit cell proliferation but the mechanism of regulation of cell proliferation by queuine or Q-tRNA is not well understood. Therefore, in the present study regulation in cell proliferation by queuine in vivo and in vitro as well as the expression of cell death regulatory protein Bcl2 are investigated. For this DLAT cancerous mouse, U87 cell line and HepG2 cell line are treated with different concentrations of queuine and the effect of queuine on cell proliferation and apoptosis are studied. The results indicate that queuine down regulates cell proliferation and expression of Bcl2 protein, suggesting that queuine promotes cell death and participates in the regulation of cell proliferation.

Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer

“…The effect of queuine on in vitro and in vivo cell proliferation has been reported previously by Pathak et al [31].…”

“…About 1 × 10 6 ascites cells in PBS (pH 7.4) were introduced intraperitoneally to each mouse as described previously [31,38].…”

“…Earlier reports have suggested that hyper-modified nucleosides found in the tRNA anticodon contribute to the high fidelity of codon recognition and influence translation [29]. Apart from its classical role, queuine has other important roles in the regulation of cell proliferation [30,31], differentiation [18], control of aerobic/anaerobic metabolism [32,33], protection from oxidative stress and oxidative radicals [34], down-regulation in the expression of proto-oncogenes [35,36] and modulation of signal-transduction pathways [37,38].…”

Characterization of the human tRNA-guanine transglycosylase: Confirmation of the heterodimeric subunit structure

“…In contrast to eubacteria, eukaryotes cannot synthesize queuine de novo and are required to obtain queuine from diet or gut flora as a nutrient factor (Reyniers et al 1981). Although its physiological role is largely unclear, queuine modification of tRNA has been suggested to be involved in cell differentiation, proliferation, and response to oxidative stress (Langgut et al 1993;Reisser et al 1994;Pathak et al 2007). In addition, it was reported that queuine-and tyrosine-deficient mice showed severe abnormalities such as labored breathing, seizures, and even death in some cases (Marks and Farkas 1997).…”

Modulation in the activity of lactate dehydrogenase and level of c-Myc and c-Fos by modified base queuine in cancer

“…Queuine is found to downregulate the level of cell death regulatory protein Bcl-2, suggesting that queuine promotes cell death and participates in the regulation of cell proliferation. 34 Mutation in proto-oncogenes and aberrant activation in RTKs enhance signaling capacity, which may lead to malignant transformation. Queuine reflects the regulation of receptor tyrosine kinase as well as receptor associated cytosolic tyrosine kinase (JAK kinase) activities.…”