Abstract
AbstractBiomarkers of cancer have made a strong traipse in predicting the disease pattern and contributed significantly to the understanding of tumour state, progression, characteristics and response to therapies. Polyamines such as putrescine, spermine and spermidine are cationic biomolecules essential for the cell cycle function and serve as excellent biomarkers of tumour progression. The polyamine biosynthesis is tightly regulated by ornithine decarboxylase, a highly inducible enzyme specific to pH, temperature, time and substrate concentration. The expression of this enzyme is very high during cell transformation and tumour progression leading to elevated level of polyamines. To measure the activity of ornithine decarboxylase an improved, easy, simple, reliable and cost-effective method has been developed utilizing small quantity of chemicals. The methodology is based on the cognizance that enzyme transforms L-ornithine hydrochloride substrate to a yellow coloured product putrescine soluble in pentanol, the absorbance of which was measured spectrophotometrically. The procedure is being utilized for evaluating cancer chemopreventive efficacy of phytomolecules. We have analyzed hundreds of molecules belonging to flavonoid, terpenes and alkaloid groups and very few were found to inhibit enzyme activity in a concentration dependent manner (0.4-50µg/mL). In addition, the molecules were also tested for their radical scavenging properties. Our results depict that molecules having phenolic groups and lactone rings in their structure are better inhibitors than their counterparts. The comparative analysis of the groups reassures flavonoids as better scavengers of radical formation and a positive correlation was observed among the nitric oxide and 2, 2-diphenyl-1-picrylhydrazyl inhibition (p<0.01). Further evaluation and augmentation may reveal novel ornthine decarboxylase inhibitors and cancer chemopreventive agents from plants.
Highlights
Biomarkers of cancer has made a strong traipse in Biomarker patent filings predicting the disease pattern and contributed significantly to the understanding of tumour state, according to type of cancer progression, characteristics and response to therapies
5-phosphate (PLP)-dependent decarboxylation of ornithine to putrescine, the first critical step in biosynthetic pathway of polyamines. Expression of this enzyme is transiently increased upon stimulation by growth factors, but becomes constitutively activated during cell transformation induced by carcinogens, viruses or oncogenes
Lots of research says that the phytomolecules having antioxioxidant property may have antimutagenic or anticarcinogenic activity
Summary
Biomarkers of cancer has made a strong traipse in Biomarker patent filings predicting the disease pattern and contributed significantly to the understanding of tumour state, according to type of cancer progression, characteristics and response to therapies. 5-phosphate (PLP)-dependent decarboxylation of ornithine to putrescine, the first critical step in biosynthetic pathway of polyamines. Upon stimulation by growth factors, but becomes constitutively activated during cell transformation induced by carcinogens, viruses or oncogenes. Lots of research says that the phytomolecules having antioxioxidant property may have antimutagenic or anticarcinogenic activity. A need is there to REFERENCE find their interactive mode on known signature Analytical Biochemistry (1987)160:290-293 markers of cancer like ornithine decarboxylase Biochem.Biophys.Res.Comm.(1994)201:748-755 enzyme
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