Abstract
In the previous study, we have found that the cordycepin which was extracted from Cordyceps mycelia produced by growing Cordyceps militaris on the dead larva of Bombyx mori silkworms showed the anti-proliferative effect toward lung cancer cells without toxicity to non-cancer cells. In this work, the cordycepin was tested for its in vitro mutagenicity and in vivo toxicity. From the Ames test and subacute toxicity test using oral administration in a rat model, the cordycepin was proved to be a non-mutagenic and non-toxic compound. The hematology and blood chemistry as well as the microanatomical characteristic of the tissues of rats fed with cordycepin every day for consecutive 30 days were comparable to those of the normal ones. Then, the cordycepin was incorporated in gelatin type A (GA) and gelatin type B (GB) nanoparticles aimed to sustain its release and activity. The cordycepin incorporated in both GA and GB nanoparticles showed the sustained release profiles. GA nanoparticles could encapsulate cordycepin at higher encapsulation efficiency due to the attractive electrostatic interaction between the positive-charged GA and the negative-charged cordycepin. However, GA nanoparticles released cordycepin at the higher amount possibly because of the large surface area of small size nanoparticles. Comparing to GB nanoparticles, the higher amount of cordycepin released from GA nanoparticles showed the higher anti-proliferative and anti-migratory effects on A549 lung cancer cells. In conclusion, GA nanoparticles were suggested as a suitable carrier for the sustained release of cordycepin. The GA nanoparticles releasing cordycepin could be an effective and non-invasive material for the treatment of lung cancer cells.
Highlights
Lung cancer has recently been the major cause of death worldwide [1]
In our recent work, we have found that the Cordyceps mycelia could be produced by growing C. militaris on the dead larva of B. mori silkworms [16]
We have previously shown that the cordycepin extracted had an antiproliferative potential toward human non-small cell lung cancer NCI-H460 cells and human lung adenocarcinoma epithelial A549 cell line due to the disruption of cell membrane by cordycepin [16]
Summary
Lung cancer has recently been the major cause of death worldwide [1]. In 2012, there were 1.59 million deaths due to the lung cancer, accounting for about 20% of cancer-related deaths [2]. High dose of drugs is required to kill lung cancer cells. Some botanically derived compounds have potential efficacy in the treatment of lung cancer with minimal side effects [6,7]. Their mechanisms against lung cancer cells including alkylating agents, topoisomerase poisons, DNA synthesis inhibitors, protein synthesis inhibitors, immunoceuticals, and lipoxygenase inhibitors are reported [6]. Cordyceps mushroom is a genus of ascomycete fungi that are mainly found on insects and other arthropods [8] It has been used as traditional Chinese medicine to treat various types of cancer for centuries [9]. Cordycepin (3-deoxyadenosine, C10H13N5O3) is a nucleoside analogue compound that shows selective anti-cancer effects [10,11,12,13]
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