Superoxide anion (O2.-) was photogenerated upon illumination of riboflavin in fluorescent light. The rate of O2.- formation was stimulated by double stranded DNA but not by denatured DNA or RNA. Depurinated DNA, which was predominantly depleted in guanine residues, did not exhibit the stimulatory effect, indicating an interaction of riboflavin, or active oxygen species derived from it, with guanine bases. Also, the stimulation of O2.- photogeneration was not observed with ethidium bromide but was seen with proflavin-intercalated DNA. Since ethidium bromide intercalates preferentially between purines and pyrimidines, and proflavin prefers dA-dT rich sites, these results were interpreted to suggest that the interaction of riboflavin with DNA is mainly with GC or CG base pairs.
The present review deals with the genetic implications of reactive oxygen species (ROS) to enhance horizons of chemophototherapy toward novel approaches for the treatment of various cancers. ROS are species of oxygen which are in a more reactive state than molecular oxygen. ROS play essential roles in vivo such as redox regulation, gene expression, immune response and many other cellular events. ROS generated by anticancer drugs during chemophototherapy may be associated with the activation of signal molecules like PKC, transcription factor NF-kappaB as well as destabilization of mitochondrial membrane inducing the release of apoptosis inducing agents like cytochrome c, resulting in toxicity to cancer cells. Thus, we suggest that anticancer drugs on exposure to light may generate oxidative stress following Fenton-like reaction generating hydroxyl radical. This may get on specific cell cycle receptors which may lead to cell cycle arrest and subsequently cytotoxic death of cancer cells.
Diabetes mellitus (DM), which influences individuals of more or less all age groups, is a crucial health concern globally characterized mainly by hyperglycemia. Advanced glycation end products are generated when non-enzymatic protein glycation occurs under hyperglycaemic circumstances. AGEs circulate in the body that increase ROS formation which activates a number of harmful pathways. Plant-derived remedies (herbal products) have been in use for centuries for treatment of many disorders. Phenolic acids are active constituents of phytochemicals. In this comparative study we have used three isomers of coumaric acid namely ortho coumaric acid (oCA), meta coumaric acid (mCA) and para coumaric acid (pCA) to deduce which one could be better problem-solving entity. HSA was used as model protein. It was glycated with glucose, with and without isomers for 28 days. We did some spectroscopic studies like UV- visible, fluorescence and CD spectroscopy. Along with spectroscopic studies some biochemicals studies like fructosamine analysis, free lysine estimation free thiol group estimation and free carbonyl group estimation were also done. To investigate the ROS production, we did fluorescence microscopy of isolated lymphocytes using DAPI and DCFH-DA. It was found that in glycated protein samples the level of absorbance and fluorescence increased along with loss of secondary structure which recovered when increasing concentration of isomers were present in glycation reaction. Amount of fructosamine and carbonyl group were also elevated in glycated sample but normalised upon treatment. Free lysine group and thiol group were also found diminished in glycated samples while they gradually recovered in treated samples. ROS production was visualized using DCFH-DA in lymphocyte treated with glycated sample, which was huge as compared to lymphocytes treated with native sample. ROS production was reduced in lymphocyte when exposed to coumaric acid treated protein samples. DAPI was used to visualise the apoptotic condition in treated lymphocytes. pCA was found consistently a better antioxidant and antiglycating agent. Our next step is to evaluate this study in animal model.
Pancreatic cancer is characterized by late detection, resistance to therapy, poor prognosis, and an exceptionally high mortality rate. Epidemiology ascribes a chemopreventive role to vitamin D in several cancers including pancreatic cancer. Vitamin D therapy has been ascribed a role previously in tumor inhibition and differentiation in addition to reduction of inflammation and angiogenesis. However, the role of vitamin D in pancreatic cancer prevention or therapy remains elusive to date. Studies have shown a negative correlation between the risk of pancreatic cancer and serum vitamin D levels. It is believed that vitamin D binding to certain conserved sequences called vitamin D response elements in the DNA can alter the expression of genes involved in tumorigenesis. Recent research has elucidated the role of zinc in carcinogenesis, which in turn is found to be affected by vitamin D supplementation. In the light of numerous new-found roles for vitamin D, we review and evaluate the potential actions of the sunshine vitamin with respect to pancreatic cancer prevention and therapy.
Quercetin is a natural polyphenolic compound that acts as a strong antioxidant for reactive oxygen species (ROS) generated by any physical or chemical action.