JOURNAL ARTICLE

Involvement of autophagy in cordycepin-induced apoptosis in human prostate carcinoma LNCaP cells

Hye Hyeon Lee, Sung Ok Kim, Gi-Young Kim, Sung-Kwon Moon, Wun-Jae Kim, Yong Kee Jeong, Young Hyun Yoo, Yung Hyun Choi
Environmental Toxicology and Pharmacology 2014, 38 (1): 239-50
24973666
Cordycepin, an active ingredient of the insect fungus Cordyceps spp., shows strong antioxidant and anticancer activities. Several molecular mechanisms have been attributed to its inhibitory effects on a wide range of tumor cells; however, the mechanism causing cancer cell death is still obscure. For the current study, we further investigated the mechanism responsible for targeting cordycepin-induced cell death and its association with autophagy in human prostate carcinoma LNCaP cells. Our results show that cordycepin resulted in significant reduction in LNCaP cell survival by inducing apoptotic cell death. Cordycepin treatment caused a dose-dependent increase of pro-apoptotic Bax and decrease of anti-apoptotic Bcl-2, triggering collapse of the mitochondrial membrane potential and activation of caspase-9 and -3. Cordycepin-induced cell death was also associated with induction of Fas and death receptor 5, activation of caspase-8, and truncation of Bid (tBid), suggesting that tBid might serve to connect activation of both the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic apoptotic pathways. The general caspase inhibitor, z-VAD-fmk, completely abolished cordycepin-induced cell death, demonstrating that cordycepin-induced apoptosis was dependent on the activation of caspases. Cordycepin also stimulated autophagy, which was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3-II, and elevation of autophagic flux; however, blockage of autophagic flux by the autophagic inhibitor bafilomycin A1 promoted cell-switching to apoptotic cell death. These findings suggest that cordycepin-induced autophagy functions as a survival mechanism and that autophagy is a potential strategy for treating prostate cancer that is resistant to pro-apoptotic therapeutics.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
24973666
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"