Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells

Abstract

Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.

Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells

“…These results indicate that such reductions of anti-apoptotic proteins may explain, at least in part, why CQ promoted TRAIL-induced apoptosis. However, our results contradict those of other reports indicating that activation of drug-mediated autophagy promotes the degradation of cFLIP and other anti-apoptotic proteins, triggering apoptosis and/or increasing TRAIL-sensitivity [ 35 – 37 ]. The cited studies used human non-small-cell lung cancer cells, whereas we utilized human pancreatic cancer cell lines.…”

Fermented Herbal Decoction Selectively Targeting Human Cancer Cell Line and Human Pathogenic Microorganism

“…In the FHD group, there were no significant mean changes in Biochemical parameter between baseline and post-treatment [49] [50]. …”

<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>

“…Traditional Chinese medicine is one of them for complementary and alternative therapy. Cordycepin, an active compound extracted from one Traditional Chinese medical herb, Cordyceps militaris, has been studied to treat many cancers including lung cancer (50), ovarian cancer (46), leukemia (30), breast cancer (47), brain cancer (19), colon cancer (27), liver cancer (25), and so on (33). Recently, some efforts have been done to investigate the po- PTEN/PI3K/Akt signaling pathway is an important pathway regulated by microRNA-21 (7).…”

“…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.…”