PMID- 27225448 OWN - NLM STAT- MEDLINE DCOM- 20170601 LR - 20170601 IS - 1875-5992 (Electronic) IS - 1871-5206 (Linking) VI - 17 IP - 1 DP - 2017 TI - Cordycepin Affects Multiple Apoptotic Pathways to Mediate Hepatocellular Carcinoma Cell Death. PG - 143-149 AB - BACKGROUND: Cordycepin possesses anti-inflammatory, anti-metastatic and anti-tumor properties. OBJECTIVE: The present study investigates the anti-hepatocellular carcinoma activities of cordycepin in in vitro and in vivo models. METHOD: Cell viability, apoptosis rate, intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide bromide assay, annexin V/propidium iodide double staining, 2',7'-dichlorfluorescein-diacetate and 5,5',6,6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining respectively. The expressions of pro-apoptosis and antiapoptosis proteins were detected by western blot. A PLC/PRL/5-xenografted nude mouse model was applied to further confirm the anti-tumor activities of cordycepin. RESULTS: Cordycepin suppressed cell viability, enhanced apoptotic rate, inhibited cell proliferation and increased cleaved poly (ADP-ribose) polymerase (PARP) level. Apoptotic alteration on mitochondria and abnormal changes on b-cell lymphoma 2 (Bcl-2) and b-cell lymphoma-extra large (Bcl-xL) levels were observed in cordycepin-treated cells. Furthermore, cordycepin suppressed the activation of extracellular signaling-regulated kinase (ERKs) and mammalian target of rapamycin (mTOR) in both PLC/PRF/5 and HepG2 cells. Finally, PLC/PRL/5-xengrafted BALB/c athymic nude mice were performed to confirm cordycepin's anti-tumor action. CONCLUSION: Our finding suggests that the anti-hepatocellular carcinoma properties of cordycepin are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways. Our study provides an experimental evidence for cordycepin as a rational agent for hepatocellular carcinoma treatment. FAU - Zhou, Yulin AU - Zhou Y FAU - Guo, Zhihua AU - Guo Z FAU - Meng, Qingfan AU - Meng Q FAU - Lu, Jiahui AU - Lu J FAU - Wang, Ning AU - Wang N FAU - Liu, Hui AU - Liu H FAU - Liang, Qiming AU - Liang Q FAU - Quan, Yutong AU - Quan Y FAU - Wang, Di AU - Wang D AD - School of Life Sciences, Jilin University, Changchun City, Jilin Province, PR China. China. FAU - Xie, Jing AU - Xie J LA - eng PT - Journal Article PL - Netherlands TA - Anticancer Agents Med Chem JT - Anti-cancer agents in medicinal chemistry JID - 101265649 RN - 0 (Antineoplastic Agents) RN - 0 (Deoxyadenosines) RN - 0 (Reactive Oxygen Species) RN - GZ8VF4M2J8 (cordycepin) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology/*therapeutic use MH - Apoptosis/*drug effects MH - Carcinoma, Hepatocellular/*drug therapy/metabolism/pathology MH - Cell Survival/drug effects MH - Deoxyadenosines/pharmacology/*therapeutic use MH - Hep G2 Cells MH - Humans MH - Liver/drug effects/metabolism/pathology MH - Liver Neoplasms/*drug therapy/metabolism/pathology MH - Male MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Mitochondria/drug effects/metabolism/pathology MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects EDAT- 2016/05/27 06:00 MHDA- 2017/06/02 06:00 CRDT- 2016/05/27 06:00 PHST- 2016/02/02 00:00 [received] PHST- 2016/03/26 00:00 [revised] PHST- 2016/05/25 00:00 [accepted] PHST- 2016/05/27 06:00 [pubmed] PHST- 2017/06/02 06:00 [medline] PHST- 2016/05/27 06:00 [entrez] AID - ACAMC-EPUB-75959 [pii] PST - ppublish SO - Anticancer Agents Med Chem. 2017;17(1):143-149.