Chou S.-M.Lai W.-J.Hong T.-W.Lai J.-Y.Tsai S.-H.Chen Y.-H.Yu S.-H.Kao C.-H.Chu R.Ding S.-T.TSAI-KUN LIShen T.-L.2022-03-142022-03-1420140944-7113https://www.scopus.com/inward/record.uri?eid=2-s2.0-84907189277&doi=10.1016%2fj.phymed.2014.07.014&partnerID=40&md5=9793450647e0f6555549cc40fec1e950https://scholars.lib.ntu.edu.tw/handle/123456789/597265Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia (CMMY) and cultivated fruiting bodies (CMFB). We found that CMFBexhibited a greater cytotoxic effect against various cancer cells over CMMY. Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by CMFBtreatment but only slightly induced by same concentration of CMMYtreatment in human HL-60 leukemia cells. Cordycepin in CMFB(10.47 mg/g) is significantly higher (?15.2 times) than that of CMMY(0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of CMMYand cordycepin. By complementing cordycepin into CMMYto the level comparable with CMFB, we observed that CMMY(500 μg/ml) with cordycepin (4.8 μg/ml) induced apoptosis to a level similar to that induced by CMFB(500 μg/ml). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of CMFBover CMMY. ? 2014 Elsevier GmbH.Apoptosis; Cancer-cell killing; Cordycepin; Cordyceps militaris; Leukemia; Synergistic[SDGs]SDG3adenosine; caspase 3; cordycepin; Cordyceps militaris extract; fungal extract; hot water; mannitol; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; unclassified drug; antineoplastic agent; cordycepin; deoxyadenosine derivative; analytic method; antineoplastic activity; antiproliferative activity; apoptosis; Article; cancer inhibition; cell killing; cell survival; cell viability; chemical composition; colorectal cancer cell line; Cordyceps; cytotoxicity; DNA fragmentation; DNA fragmentation assay; down regulation; drug potentiation; enzyme activation; fluorescence microscopy; fruiting body; high performance liquid chromatography; human; human cell; humidity; immunoblotting; isobolographic analysis; leukemia cell line; liver cancer cell line; MTT assay; mycelium; phenotype; prostate cancer cell line; protein cleavage; apoptosis; cell proliferation; chemistry; Cordyceps; drug effects; HL 60 cell line; Antineoplastic Agents; Apoptosis; Cell Proliferation; Cordyceps; Deoxyadenosines; HL-60 Cells; Humansjournal article10.1016/j.phymed.2014.07.014254422602-s2.0-84907189277