<b>Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN </b><b>phosphatase </b>

Abstract

Cordycepin is an active component extracted from Traditional Chinese medical herb Cordyceps militaris. Many reports demonstrated that cordycepin harbors antitumor activity in a broad spectrum of cancer types. In this study the actions and the underneath molecular mechanisms of cordycepin were investigated in renal cell carcinoma Caki-1 cell line. Results showed that cordycepin induced apoptotic cell death and inhibited cell migration in Caki-1 cells. Quantitative real-time PCR results and western blot analyses indicated cordycepin dose-dependently decreased microRNA-21 expression and Akt phosphorylation levels in Caki-1 cells, but increased PTEN phosphatase levels. Block of cordycepin-induced microRNA-21 decrease or PTEN increase in Caki-1 cells by transfection of microRNA-21 mimic or PTEN siRNA significantly attenuated cordycepin-induced cell death and inhibition of cell migration. Taken together, findings in present study suggested that cordycepin induced apoptotic cell death in renal cell carcinoma through regulation of microRNA-21 and PTEN phosphatase. Furthermore, present study also firstly illustrated that cordycepin inhibited cell migration of renal cell carcinoma, which also involved micro-RNA-21 and PTEN phosphatase.Renal cell carcinoma (RCC) is the most lethal urological cancer, accounting for 87% of all renal malignancies and 2-3% of all cancers (4). In the past two decades, the global incidence of RCC has increased by 2% per year (4). Worldwide, the agestandardized incidence and mortality of RCC were 6 per 100,000 and 2.1 per 100,000 respectively (43). Despite advance in diagnostic techniques, up to 20-30% of patients with RCC present with metastasis (4). The prognosis of RCC has historically been poor, with 5-year survival rate of 8% among patients with metastatic RCC (9). Although recent progress about understanding of the pathogenesis of RCC has led to novel immune-based and targeted treatments for this chemoresistant cancer, no one drug obtains overall response rate of 100% and durable complete responses (4, 9). Development of neo-adjuvant therapy is still in a demand at present. Cordycepin is a main active composition extracted from Cordyceps militaris and has been reported to harbor anti-tumor activity in a broad spectrum of cancer types, including lung cancer (50), ovarian cancer (46), leukemia (30), breast cancer (47), and so on (33). Two recent reports firstly demonstrated that cordycepin could induce apoptosis in renal cell carcinoma through Erk-JNK signaling pathway (20,48) and indicated the potential application of cordycepin in treating renal cell carcinoma. However, the actions and the underneath molecular mechanisms of cordycepin in renal cell carcinoma are not definitely clear and warrant extensive and further investigations. Recently, a comprehensive molecular analysis

Cordycepin Accelerates Osteoblast Mineralization and Attenuates Osteoclast Differentiation In Vitro

“…We further examined the effect of cordycepin on OSCAR, cathepsin K and MMP9 mRNA expression levels, where 1 μ M cordycepin significantly downregulated RANKL-induced OSCAR, cathepsin K and MMP activation (Figures 5(c) , 5(d) and 5(e) ). Plus, NFATc1 and cFOS activation were caused by MAPK (mitogen-activated protein kinases) signaling, which is required for early osteoclast differentiation [ 28 , 29 ]. To confirm the molecular mechanism of cordycepin effects on MAPKs following the activation of RANKL in RAW264.7 cells, we investigated the phosphorylation of p38, ERK and JNK using a western blot.…”

“…Several research studies have reported that cordycepin plays a function in a multitude of pathologic and physiologic processes, including tumor metastasis, vascular disorder, and brain function [ 28 – 31 ]. Regarding bone metabolism, cordycepin has been used to prevent oxidative stress-induced bone loss [ 23 , 32 ].…”

MicroRNA‑26a protects vascular smooth muscle cells against H2O2‑induced injury through activation of the PTEN/AKT/mTOR pathway

“…Primary vascular smooth muscle cells (VSMCs) were isolated and obtained using a technique combining explant culture and enzymatic digestion from the abdominal aorta of five male Sprague-Dawley rats (age, 3-4 weeks; weight, 80±20 g) obtained from the Laboratory Animal Center of Hebei Medical University (Shijiazhuang, China) as described previously ( 21 ). All animals were housed in a 12 h light/dark schedule in a temperature (22±2°C) and humidity (<40%) controlled room with free access to food and water.…”

Role of MicroRNAs Induced by Chinese Herbal Medicines Against Hepatocellular Carcinoma: A Brief Review

“… 32 Cordycepin, an adenosine analogue isolated from Cordyceps militaris , downregulated miRNA-21 expression, and thus induced apoptotic cell death and inhibited cell migration in renal cell carcinoma Caki-1 cell line. 33 Therefore, Chinese herbal medicines such as ginsenoside Rb1 and cordycepin may have antitumor activity in a broad spectrum of cancer types through the regulation of specific miRNAs.…”

“… 41 , 42 Cordycepin isolated from Cordyceps militaris could downregulate miRNA-21 expression, and induce apoptotic cell death and inhibit cell migration in renal cell carcinoma cells. 33 It is possible that cordycepin may suppress HCC development through the downregulation of miRNA-21. Similarly, miRNA-25 was also significantly upregulated in HCC clinical samples and stimulated HCC cell growth, migration, and invasion.…”