Physical shearing imparts biological activity to DNA and ability to transmit itself horizontally across species and kingdom boundaries.

BACKGROUND: We have recently reported that cell-free DNA (cfDNA) fragments derived from dying cells that circulate in blood are biologically active molecules and can readily enter into healthy cells to activate DNA damage and apoptotic responses in the recipients. However, DNA is not conventionally known to spontaneously enter into cells or to have any intrinsic biological activity. We hypothesized that cellular entry and acquisition of biological properties are functions of the size of DNA. RESULTS: To test this hypothesis, we generated small DNA fragments by sonicating high molecular weight DNA (HMW DNA) to mimic circulating cfDNA. Sonication of HMW DNA isolated from cancerous and non-cancerous human cells, bacteria and plant generated fragments 300-3000 bp in size which are similar to that reported for circulating cfDNA. We show here that while HMW DNAs were incapable of entering into cells, sonicated DNA (sDNA) from different sources could do so indiscriminately without heed to species or kingdom boundaries. Thus, sDNA from human cells and those from bacteria and plant could enter into nuclei of mouse cells and sDNA from human, bacterial and plant sources could spontaneously enter into bacteria. The intracellular sDNA associated themselves with host cell chromosomes and integrated into their genomes. Furthermore, sDNA, but not HMW DNA, from all four sources could phosphorylate H2AX and activate the pro-inflammatory transcription factor NFκB in mouse cells, indicating that sDNAs had acquired biological activities. CONCLUSIONS: Our results show that small fragments of DNA from different sources can indiscriminately enter into other cells across species and kingdom boundaries to integrate into their genomes and activate biological processes. This raises the possibility that fragmented DNA that are generated following organismal cell-death may have evolutionary implications by acting as mobile genetic elements that are involved in horizontal gene transfer.

Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer.

Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties. In vitro and in vivo studies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems.