Cordycepin Affects Multiple Apoptotic Pathways to Mediate Hepatocellular Carcinoma Cell Death

Title:Cordycepin Affects Multiple Apoptotic Pathways to Mediate Hepatocellular Carcinoma Cell Death

Volume: 17 Issue: 1

Author(s): Yulin Zhou, Zhihua Guo, Qingfan Meng, Jiahui Lu, Ning Wang, Hui Liu, Qiming Liang, Yutong Quan, Di Wang and Jing Xie

Affiliation:

Keywords: Apoptosis, Apoptotic pathways, Cordycepin, Hepatocellular carcinoma.

Abstract: 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.

Cite this article as:

Zhou Yulin, Guo Zhihua, Meng Qingfan, Lu Jiahui, Wang Ning, Liu Hui, Liang Qiming, Quan Yutong, Wang Di and Xie Jing, Cordycepin Affects Multiple Apoptotic Pathways to Mediate Hepatocellular Carcinoma Cell Death, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1871520616666160526114555