An Anti-Cancer Cordycepin Produced by Cordyceps militaris Growing on the Dead Larva of Bombyx mori Silkworm

In this study, we introduced the dead pupa and larva of Bombyx mori silkworms as nutrition medium for the growing of different fungi including Cordyceps militaris, Isaria tenuipes and Isaria farinose to produce Cordyceps mycelia and anti-cancer cordycepin. The anti-proliferative and anti-migratory activities of cordycepin extracted toward cancer cells were investigated. We found that the dead silk larva which contained high carbohydrate and moisture but low fat content could be a good host for the growth of Cordyceps militaris and Isaria tenuipes to produce Cordyceps. The cordycepin extracted from Cordyceps mycelia of Cordyceps militaris grown on dead silk larva showed the highest anti-proliferative potential toward human non-small cell lung cancer NCI-H460 cells with a half maximal inhibitory concentration (IC50) of 0.7 µM. Furthermore, the viability of human lung adenocarcinoma epithelial A549 cell line remained < 20% while that of human airway epithelial Calu-3 cell line was < 40% after treated with the cordycepin extracted (0.125-2 µM) due to the disruption of cell membrane by cordycepin. We also found that our cordycepin (0.25-2 µM) could inhibit the migration of A549 cells. On the other hand, the cordycepin was not toxic to small airway epithelial cells (SAEC) of non-cancer cells. Therefore, Cordyceps militaris grown on the dead larva of B. mori silkworms was introduced as a promising source for the production of Cordyceps mycelia and anti-cancer cordycepin without toxicity to non-cancer cells.