Chou S.-M.Lai W.-J.Hong T.Tsai S.-H.Chen Y.-H.Kao C.-H.Chu R.Shen T.-L.TSAI-KUN LI2022-03-142022-03-1420150192-415Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84940460889&doi=10.1142%2fS0192415X15500603&partnerID=40&md5=75c4c3d5e245235b11e11caae90a5075https://scholars.lib.ntu.edu.tw/handle/123456789/597262Cordyceps militaris is a traditional Chinese medicine frequently used for tonic and therapeutic purposes. Reports from our laboratory and others have demonstrated that extracts of the cultivated fruiting bodies of C. militaris (CM) exhibit a potent cytotoxic effect against many cancer cell lines, especially human leukemia cells. Here, we further investigated the underlying mechanism through which CM is cytotoxic to cancer cells. The CM-mediated induction of PARP cleavage and its related DNA damage signal (γH2AX) was diminished by caspase inhibitor I. In contrast, a ROS scavenger failed to prevent CM-mediated leukemia cell death. Moreover, two signaling molecules, AKT and p38 MAPK, were activated during the course of apoptosis induction. Employing MTT analysis, we found that a p38 MAPK inhibitor but not an AKT inhibitor could rescue cells from CM-mediated cell death, as well as inhibit the cleavage of PARP, formation of apoptotic bodies and up-regulation of the γH2AX signal. These results suggest that CM-mediated leukemia cell death occurs through the activation of the p38 MAPK pathway, indicating its potential therapeutic effects against human leukemia. ? 2015 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.Anti-Leukemia; Apoptosis; Cell Signaling; Cordyceps militaris; DNA Damage; p38 MAPK[SDGs]SDG32 morpholino 8 phenylchromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; caspase inhibitor; cordyceps militaris extract; fungal extract; gamma histone h2ax; histone H2AX; mitogen activated protein kinase p38; mitogen activated protein kinase p38 inhibitor; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein kinase B; protein kinase B inhibitor; reactive oxygen metabolite; unclassified drug; antineoplastic agent; H2AFX protein, human; herbaceous agent; histone; mitogen activated protein kinase p38; antineoplastic activity; apoptosis; Article; cancer cell line; cell death; cell viability; controlled study; Cordyceps; DNA damage; enzyme activation; human; human cell; leukemia; leukemia cell; MTT assay; protein cleavage; protein phosphorylation; signal transduction; upregulation; chemistry; Cordyceps; drug effects; drug screening; gene expression; genetics; HL 60 cell line; isolation and purification; leukemia; metabolism; pathology; physiology; procedures; Antineoplastic Agents, Phytogenic; Cordyceps; DNA Damage; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Gene Expression; Histones; HL-60 Cells; Humans; Leukemia; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Up-Regulationjournal article10.1142/S0192415X15500603262059662-s2.0-84940460889