TRAIL and microRNAs in the treatment of prostate cancer: therapeutic potential and role of nanotechnology

Abstract

Disruption of spatiotemporal behavior of intracellular signaling cascades including tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling in prostate cancer has gained tremendous attention in the past few years. There is an increasing effort in translating the emerging information about TRAIL-mediated signaling obtained through experimental and preclinical data to clinic. Fascinatingly, novel targeting approaches are being developed to enhance the tissue- or subcellular-specific delivery of drugs with considerable focus on prostate cancer. These applications have the potential to revolutionize prostate cancer therapeutic strategies and include the accumulation of drugs in target tissue as well as the selection of internalizing ligands for enhanced receptor-mediated uptake of drugs. In this mini-review, we outline outstanding developments in therapeutic strategies based on the regulation and/or targeting of TRAIL pathway for the treatment of prostate cancer. Moreover, microRNAs (miRNAs), with potential transcriptional and posttranscriptional regulation of gene expression, will be presented for their potential in prostate cancer treatment. Emphasis has been given to the use of delivery approaches, especially based on nanotechnology. Considerably, enhanced information regarding miRNA regulation of TRAIL-mediated signaling in prostate cancer cells may provide potential biomarkers for the characterization of patients as responders and nonresponders of TRAIL-based therapy and could provide rationalized basis for combination therapies with TRAIL death receptor-targeting drugs.

Upregulation of microRNA135a-3p and death receptor 5 plays a critical role in Tanshinone I sensitized prostate cancer cells to TRAIL induced apoptosis

“…Thus, Farooqi et al [3] suggested that miRNA regulation of TRAIL-mediated signaling in prostate cancer cells can provide potential biomarkers for the characterization of patients as responders and non-responders for TRAIL-based therapy. Recently, miR-135a was also reported to inhibit the proliferation of renal carcinoma [19], induce apoptosis in gastric cancer cells [48] and promote drug sensitivity in cancer cells[49].…”

“…Though anti-cancer drugs such as Eulexin, Flutamide and Nilandron have been used for treatment of prostate cancer, their side effects have still occurred. Recent studies reported that TRAIL and microRNA (miR)s were suggested as potential biomarker or therapeutic potential in prostate cancer cells [3]. …”

Study of Thermal Degradation of PLGA, PLGA Nanospheres and PLGA/Maghemite Superparamagnetic Nanospheres

“…Cancer is a multifaceted and genomically complex disease and rapidly emerging experimental evidence has started to shed light on wide ranging factors which underlie cancer development and progression. Confluence of information suggested various nanotechnological approaches to enhance delivery of anticancer agents to the tumor site [14][15][16][17] . Still, because of the degradation ability of PLGA, these materials can be drug carriers, which will, in turn, be released in these specific locations, thus decreasing the side effects caused by medicines to normal cells [11][12][13] .…”

Nanotechnology - A Path to a Sustainable Future

“… Nanoscale devices which are smaller than 50 nanometers can without issues enter most cells, while those smaller than 20 nanometers can circulate out of blood vessels as they circulate via the frame.  Nanoscale gadgets have the capability to substantially alternate cancer remedy for the higher and to dramatically growth the quantity of exceedingly effective therapeutic agents [86][87][88] .  Nanoscale constructs, for instance, have to characteristic customizable, targeted drug delivery cars capable of ferrying big doses of chemotherapeutic stores or healing genes into malignant cells even as sparing healthful cells, which may greatly, lessen or get rid of the frequently unpalatable facet effects that accompany many contemporary most cancers healing tactics [89,90] .…”