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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

General Review Article

Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects

Author(s): Md. Asaduzzaman Khan* and Mousumi Tania*

Volume 27, Issue 6, 2020

Page: [983 - 996] Pages: 14

DOI: 10.2174/0929867325666181001105749

Price: $65


Background: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which occupies a notable place in traditional medicine.

Objective: In this review article, we have discussed the recent findings on the molecular aspects of cordycepin interactions with its recognized cellular targets, and possible mechanisms of its anticancer activity.

Methods: We have explored databases like pubmed, google scholar, scopus and web of science for the update information on cordycepin and mechanisms of its anticancer activity, and reviewed in this study.

Results: Cordycepin has been widely recognized for its therapeutic potential against many types of cancers by various mechanisms. More specifically, cordycepin can induce apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill or control cancer cell growth. Also cordycepin can induce autophagy and modulate immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although many success stories of cordycepin in anticancer research in vitro and in animal model, and there is no successful clinical trial yet.

Conclusion: Ongoing research studies have reported highly potential anticancer activities of cordycepin with numerous molecular mechanisms. The in vitro and in vivo success of cordycepin in anticancer research might influence the clinical trials of cordycepin, and this molecule might be used for development of future cancer drug.

Keywords: Cordycepin, apoptosis, cell cycle, immuno-modulation, DNA damage, cancer therapeutics.

« Previous
Ng, T.B.; Wang, H.X. Pharmacological actions of Cordyceps, a prized folk medicine. J. Pharm. Pharmacol., 2005, 57(12), 1509-1519.
[] [PMID: 16354395]
Jeong, J.W.; Jin, C.Y.; Park, C.; Hong, S.H.; Kim, G.Y.; Jeong, Y.K.; Lee, J.D.; Yoo, Y.H.; Choi, Y.H. Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells. Toxicol. In Vitro, 2011, 25(4), 817-824.
[] [PMID: 21310227]
Lin, B.; Li, S. Cordyceps as an herbal drug.Herbal Medicine: Biomolecular and Clinical Aspects; 2nd ed.; Benzie, I.F.F.; Wachtel-Galor, S., Eds.; CRC Press/Taylor & Francis: Boca Raton, FL, 2011.
Steinkraus, D.C.; Whitfield, J.B. Chinese caterpillar fungus and world record runners. Am. Entomol. (Lanham Md.), 1994, 40, 235-239.
Smiderle, F.R.; Sassaki, G.L.; Van Griensven, L.J.; Iacomini, M. Isolation and chemical characterization of a glucogalactomannan of the medicinal mushroom Cordyceps militaris. Carbohydr. Polym., 2013, 97(1), 74-80.
[] [PMID: 23769519]
Hu, H.; Xiao, L.; Zheng, B.; Wei, X.; Ellis, A.; Liu, Y.M. Identification of chemical markers in Cordyceps sinensis by HPLC-MS/MS. Anal. Bioanal. Chem., 2015, 407(26), 8059-8066.
[] [PMID: 26302964]
Meng, C.; Han, Q.; Wang, X.; Liu, X.; Fan, X.; Liu, R.; Wang, Q.; Wang, C. Determination and quantitative comparison of nucleosides in two cordyceps by HPLC-ESI-MS-MS. J. Chromatogr. Sci., 2019, 57(5), 426-433.
[] [PMID: 30796779]
Chiriví, J.; Danies, G.; Sierra, R.; Schauer, N.; Trenkamp, S.; Restrepo, S.; Sanjuan, T. Metabolomic profile and nucleoside composition of Cordyceps nidus sp. nov. (Cordycipitaceae): A new source of active compounds. PLoS One, 2017, 12(6) e0179428
[] [PMID: 28636672]
Sharma, S.K.; Gautam, N. Chemical composition and antioxidant and antibacterial activities of cultured mycelia of four Clavicipitaceous Mushrooms (Ascomycetes) from the Indian Himalayas. Int. J. Med. Mushrooms, 2017, 19(1), 45-54.
[] [PMID: 28322146]
Cunningham, K.G.; Hutchinson, S.A.; Manson, W.; Spring, F.S. Cordycepin, a metabolic product from cultures of Cordyceps militaris(Linn.) link. Part I. Isolation and characterization. J. Chem. Soc., 1951, 1951, 2299-2300.
Bentley, H.R.; Cunningham, K.G.; Spring, F.S. Cordycepin, a metabolic product from cultures of Cordyceps militaris(Linn.) link. Part II. The structure of cordycepin. J. Chem. Soc., 1951, 1951, 2301-2305.
Tuli, H.S.; Sharma, A.K.; Sandhu, S.S.; Kashyap, D. Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci., 2013, 93(23), 863-869.
[] [PMID: 24121015]
Liu, Y.; Wang, J.; Wang, W.; Zhang, H.; Zhang, X.; Han, C. The chemical constituents and pharmacological actions of Cordyceps sinensis. Evid. Based Complement. Alternat. Med., 2015, 2015575063
[] [PMID: 25960753]
Khan, M.A.; Tania, M.; Zhang, D.; Chen, H. Cordyceps mushroom: a potent anticancer nutraceutical. Open Nutr. J., 2010, 3, 179-183.
De Clercq, E. Curious (old and new) antiviral nucleoside analogues with intriguing therapeutic potential. Curr. Med. Chem., 2015, 22(34), 3866-3880.
[] [PMID: 26112146]
Rich, M.A.; Meyers, P.; Weinbaum, G.; Cory, J.G.; Suhadolnik, R.J. Inhibition of human tumor cells by cordycepin. Biochim. Biophys. Acta, 1965, 95, 194-204.
[] [PMID: 14293694]
Müller, W.E.; Seibert, G.; Beyer, R.; Breter, H.J.; Maidhof, A.; Zahn, R.K. Effect of cordycepin on nucleic acid metabolism in L5178Y cells and on nucleic acid-synthesizing enzyme systems. Cancer Res., 1977, 37(10), 3824-3833.
[PMID: 332340]
Glazer, R.I.; Lott, T.J.; Peale, A.L. Potentiation by 2′-deoxycoformycin of the inhibitory effect by 3′-deoxyadenosine (cordycepin) on nuclear RNA synthesis in L1210 cells in vitro. Cancer Res., 1978, 38(8), 2233-2238.
[PMID: 307428]
Shigeura, H.T.; Gordon, C.N. The effects of 3′-deoxyadenosine on the synthesis of ribonucleic acid. J. Biol. Chem., 1965, 240, 806-810.
[PMID: 14275139]
Cholon, J.J.; Studzinski, G.P. Metabolic differences between normal and neoplastic cells: effects of aminonucleoside on cytoplasmic messenger RNA. Science, 1974, 184(4133), 160-161.
[] [PMID: 4361100]
Perez, S.; Trangas, T.; Kokkinopoulos, D.; Tsiapalis, C.M.; Papamichail, M. Polyadenylic acid metabolizing enzyme levels during induction of differentiation in a human leukemia T-cell line with phorbol ester. J. Natl. Cancer Inst., 1987, 78(3), 407-411.
[PMID: 3029496]
Richardson, L.S.; Ting, R.C.; Gallo, R.C.; Wu, A.M. Effect of cordycepin on the replication of type-c RNA tumor viruses. Int. J. Cancer, 1975, 15(3), 451-456.
[] [PMID: 166934]
Izuta, S.; Kohsaka-Ichikawa, M.; Yamaguchi, T.; Saneyoshi, M. 3′-Deoxyribonucleotides inhibit eukaryotic DNA primase. J. Biochem., 1996, 119(6), 1038-1044.
[] [PMID: 8827435 ]
Legraverend, M.; Glazer, R.I. Inhibition of the phosphorylation of non-histone chromosomal proteins of rat liver by cordycepin and cordycepin triphosphate. Cancer Res., 1978, 38(4), 1142-1146.
[PMID: 305821]
Nakamura, K.; Yoshikawa, N.; Yamaguchi, Y.; Kagota, S.; Shinozuka, K.; Kunitomo, M. Antitumor effect of cordycepin (3′-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res., 2006, 26(1A), 43-47.
[PMID: 16475677]
Yoshikawa, N.; Yamada, S.; Takeuchi, C.; Kagota, S.; Shinozuka, K.; Kunitomo, M.; Nakamura, K. Cordycepin (3′-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma cells through the stimulation of adenosine A3 receptor followed by glycogen synthase kinase-3beta activation and cyclin D1 suppression. Naunyn Schmiedebergs Arch. Pharmacol., 2008, 377(4-6), 591-595.
[] [PMID: 18084742]
Nakamura, K.; Shinozuka, K.; Yoshikawa, N. Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis. J. Pharmacol. Sci., 2015, 127(1), 53-56.
[] [PMID: 25704018]
Cao, H.L.; Liu, Z.J.; Chang, Z. Cordycepin induces apoptosis in human bladder cancer cells via activation of A3 adenosine receptors. Tumour Biol., 2017, 39(7) 1010428317706915
[] [PMID: 28714368]
Chen, Y.; Yang, S.H.; Hueng, D.Y.; Syu, J.P.; Liao, C.C.; Wu, Y.C. Cordycepin induces apoptosis of C6 glioma cells through the adenosine 2A receptor-p53-caspase-7-PARP pathway. Chem. Biol. Interact., 2014, 216, 17-25.
[] [PMID: 24704558]
Koç, Y.; Urbano, A.G.; Sweeney, E.B.; McCaffrey, R. Induction of apoptosis by cordycepin in ADA-inhibited TdT-positive leukemia cells. Leukemia, 1996, 10(6), 1019-1024.
[PMID: 8667637]
Kodama, E.N.; McCaffrey, R.P.; Yusa, K.; Mitsuya, H. Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem. Pharmacol., 2000, 59(3), 273-281.
[] [PMID: 10609556]
Thomadaki, H.; Scorilas, A.; Tsiapalis, C.M.; Havredaki, M. The role of cordycepin in cancer treatment via induction or inhibition of apoptosis: implication of polyadenylation in a cell type specific manner. Cancer Chemother. Pharmacol., 2008, 61(2), 251-265.
[] [PMID: 17487491]
Chen, L.S.; Stellrecht, C.M.; Gandhi, V. RNA-directed agent, cordycepin, induces cell death in multiple myeloma cells. Br. J. Haematol., 2008, 140(6), 682-391.
[] [PMID: 18205859]
Wang, B.J.; Won, S.J.; Yu, Z.R.; Su, C.L. Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide. Food Chem. Toxicol., 2005, 43(4), 543-552.
[] [PMID: 15721201]
He, W.; Zhang, M.F.; Ye, J.; Jiang, T.T.; Fang, X.; Song, Y. Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules. J. Zhejiang Univ. Sci. B, 2010, 11(9), 654-660.
[] [PMID: 20803769]
Lee, S.Y.; Debnath, T.; Kim, S.K.; Lim, B.O. Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29. Food Chem. Toxicol., 2013, 60, 439-447.
[] [PMID: 23941773]
Shao, L.W.; Huang, L.H.; Yan, S.; Jin, J.D.; Ren, S.Y. Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways. Oncol. Lett., 2016, 12(2), 995-1000.
[] [PMID: 27446383]
Zhou, Y.; Guo, Z.; Meng, Q.; Lu, J.; Wang, N.; Liu, H.; Liang, Q.; Quan, Y.; Wang, D.; Xie, J. Cordycepin affects multiple apoptotic pathways to mediate hepatocellular carcinoma cell death. Anticancer. Agents Med. Chem., 2017, 17(1), 143-149.
[PMID: 27225448]
Lee, H.H.; Jeong, J.W.; Lee, J.H.; Kim, G.Y.; Cheong, J.; Jeong, Y.K.; Yoo, Y.H.; Choi, Y.H. Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway. Oncol. Rep., 2013, 30(3), 1257-1264.
[] [PMID: 23828231]
Hwang, J.H.; Joo, J.C.; Kim, D.J.; Jo, E.; Yoo, H.S.; Lee, K.B.; Park, S.J.; Jang, I.S. Cordycepin promotes apoptosis by modulating the ERK-JNK signaling pathway via DUSP5 in renal cancer cells. Am. J. Cancer Res., 2016, 6(8), 1758-1771.
[PMID: 27648363]
Joo, J.C.; Hwang, J.H.; Jo, E.; Kim, Y.R.; Kim, D.J.; Lee, K.B.; Park, S.J.; Jang, I.S. Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma. Oncotarget, 2017, 8(7), 12211-12224.
[] [PMID: 28099944]
Wang, Z.; Wu, X.; Liang, Y.N.; Wang, L.; Song, Z.X.; Liu, J.L.; Tang, Z.S. Cordycepin induces apoptosis and inhibits proliferation of human lung cancer cell line H1975 via inhibiting the phosphorylation of EGFR. Molecules, 2016, 21(10) E1267
[] [PMID: 27689974]
Hwang, J.H.; Park, S.J.; Ko, W.G.; Kang, S.M.; Lee, D.B.; Bang, J.; Park, B.J.; Wee, C.B.; Kim, D.J.; Jang, I.S.; Ko, J.H. Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric oxide mediated ERK/Slug signaling pathway. Am. J. Cancer Res., 2017, 7(3), 417-432.
[PMID: 28401001]
Baik, J.S.; Kwon, H.Y.; Kim, K.S.; Jeong, Y.K.; Cho, Y.S.; Lee, Y.C. Cordycepin induces apoptosis in human neuroblastoma SK-N-BE(2)-C and melanoma SK-MEL-2 cells. Indian J. Biochem. Biophys., 2012, 49(2), 86-91.
[PMID: 22650004]
Baik, J.S.; Kim, K.S.; Moon, H.I.; An, H.K.; Park, S.J.; Kim, C.H.; Lee, Y.C. Cordycepin-mediated transcriptional regulation of human GD3 synthase (hST8Sia I) in human neuroblastoma SK-N-BE(2)-C cells. Acta Biochim. Biophys. Sin. (Shanghai), 2014, 46(1), 65-71.
[] [PMID: 24225218]
Li, Y.; Li, R.; Zhu, S.; Zhou, R.; Wang, L.; Du, J.; Wang, Y.; Zhou, B.; Mai, L. Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells. Oncol. Lett., 2015, 9(6), 2541-2547.
[] [PMID: 26137103]
Chen, Y.; Chen, Y.C.; Lin, Y.T.; Huang, S.H.; Wang, S.M. Cordycepin induces apoptosis of CGTH W-2 thyroid carcinoma cells through the calcium-calpain-caspase 7-PARP pathway. J. Agric. Food Chem., 2010, 58(22), 11645-11652.
[] [PMID: 20961042]
Wu, W.C.; Hsiao, J.R.; Lian, Y.Y.; Lin, C.Y.; Huang, B.M. The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother. Pharmacol., 2007, 60(1), 103-111.
[] [PMID: 17031645]
Lee, H.H.; Park, C.; Jeong, J.W.; Kim, M.J.; Seo, M.J.; Kang, B.W.; Park, J.U.; Kim, G.Y.; Choi, B.T.; Choi, Y.H.; Jeong, Y.K. Apoptosis induction of human prostate carcinoma cells by cordycepin through reactive oxygen speciesmediated mitochondrial death pathway. Int. J. Oncol., 2013, 42(3), 1036-1044.
[] [PMID: 23292300]
Tania, M.; Shawon, J.; Saif, K.; Kiefer, R.; Safaei Khorram, M.; Halim, M.A.; Khan, M.A. Cordycepin downregulates Cdk2 to interfere with cell cycle and increases apoptosis by generating ROS in cervical cancer cells: in vitro and in silico study. Curr. Cancer Drug Targets, 2018.
Lee, S.J.; Kim, S.K.; Choi, W.S.; Kim, W.J.; Moon, S.K. Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells. Arch. Biochem. Biophys., 2009, 490(2), 103-109.
[] [PMID: 19733546]
Lee, S.J.; Moon, G.S.; Jung, K.H.; Kim, W.J.; Moon, S.K. c-Jun N-terminal kinase 1 is required for cordycepin-mediated induction of G2/M cell-cycle arrest via p21WAF1 expression in human colon cancer cells. Food Chem. Toxicol., 2010, 48(1), 277-283.
[] [PMID: 19833164]
Seong, B.; Hong, S.; Muthusami, S.; Kim, W.D.; Yu, J.R.; Park, W.Y. Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest. Eur. J. Pharmacol., 2016, 771, 77-83.
[] [PMID: 26688569]
Wang, X.A.; Xiang, S.S.; Li, H.F.; Wu, X.S.; Li, M.L.; Shu, Y.J.; Zhang, F.; Cao, Y.; Ye, Y.Y.; Bao, R.F.; Weng, H.; Wu, W.G.; Mu, J.S.; Hu, Y.P.; Jiang, L.; Tan, Z.J.; Lu, W.; Wang, P.; Liu, Y.B. Cordycepin induces S phase arrest and apoptosis in human gallbladder cancer cells. Molecules, 2014, 19(8), 11350-11365.
[] [PMID: 25090123]
de Azevedo, W.F. Opinion paper: targeting multiple cyclin-dependent kinases (CDKs): a new strategy for molecular docking studies. Curr. Drug Targets, 2016, 17(1), 2.
[] [PMID: 26687602]
Levin, N.M.B.; Pintro, V.O.; de Avila, M.B.; de Mattos, B.B.; De Azevedo, W.F. Jr. Understanding the structural basis for inhibition of cyclin-dependent kinases. New pieces in the molecular puzzle. Curr. Drug Targets, 2017, 18(9), 1104-1111.
[] [PMID: 27848884]
Barkat, M.A. Harshita; Ahmad, J.; Khan, M.A.; Beg, S.; Ahmad, F.J. Insights into the targeting potential of thymoquinone for therapeutic intervention against triple-negative breast cancer. Curr. Drug Targets, 2018, 19(1), 70-80.
[] [PMID: 28606050]
de Ávila, M.B.; Xavier, M.M.; Pintro, V.O.; de Azevedo, W.F. Jr. Supervised machine learning techniques to predict binding affinity. A study for cyclin-dependent kinase 2. Biochem. Biophys. Res. Commun., 2017, 494(1-2), 305-310.
[] [PMID: 29017921]
Levin, N.M.B.; Pintro, V.O.; Bitencourt-Ferreira, G.; de Mattos, B.B.; de Castro Silvério, A.; de Azevedo, W.F. Jr. Development of CDK-targeted scoring functions for prediction of binding affinity. Biophys. Chem., 2018, 235, 1-8.
[] [PMID: 29407904]
Wu, K.; Yi, Y.; Liu, F.; Wu, W.; Chen, Y.; Zhang, W. Identification of key pathways and genes in the progression of cervical cancer using bioinformatics analysis. Oncol. Lett., 2018, 16(1), 1003-1009.
[] [PMID: 29963176]
Schulze-Gahmen, U.; Brandsen, J.; Jones, H.D.; Morgan, D.O.; Meijer, L.; Vesely, J.; Kim, S.H. Multiple modes of ligand recognition: crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine. Proteins, 1995, 22(4), 378-391.
[] [PMID: 7479711]
Gray, N.; Détivaud, L.; Doerig, C.; Meijer, L. ATP-site directed inhibitors of cyclin-dependent kinases. Curr. Med. Chem., 1999, 6(9), 859-875.
[PMID: 10495356]
Kim, S.H.; Schulze-Gahmen, U.; Brandsen, J.; de Azevedo Júnior, W.F. Structural basis for chemical inhibition of CDK2. Prog. Cell Cycle Res., 1996, 2, 137-145.
[] [PMID: 9552391]
De Azevedo, W.F.; Leclerc, S.; Meijer, L.; Havlicek, L.; Strnad, M.; Kim, S.H. Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem., 1997, 243(1-2), 518-526.
[] [PMID: 9030780]
Kim, H.G.; Shrestha, B.; Lim, S.Y.; Yoon, D.H.; Chang, W.C.; Shin, D.J.; Han, S.K.; Park, S.M.; Park, J.H.; Park, H.I.; Sung, J.M.; Jang, Y.; Chung, N.; Hwang, K.C.; Kim, T.W. Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur. J. Pharmacol., 2006, 545(2-3), 192-199.
[] [PMID: 16899239]
Yoon, J.Y.; Kim, J.H.; Baek, K.S.; Kim, G.S.; Lee, S.E.; Lee, D.Y.; Choi, J.H.; Kim, S.Y.; Park, H.B.; Sung, G.H.; Lee, K.R.; Cho, J.Y.; Noh, H.J. A direct protein kinase B-targeted anti-inflammatory activity of cordycepin from artificially cultured fruit body of Cordyceps militaris. Pharmacogn. Mag., 2015, 11(43), 477-485.
[] [PMID: 26246722]
Pao, H.Y.; Pan, B.S.; Leu, S.F.; Huang, B.M. Cordycepin stimulated steroidogenesis in MA-10 mouse Leydig tumor cells through the protein kinase C Pathway. J. Agric. Food Chem., 2012, 60(19), 4905-4913.
[] [PMID: 22512531]
Pan, B.S.; Wang, Y.K.; Lai, M.S.; Mu, Y.F.; Huang, B.M. Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways. Sci. Rep., 2015, 5, 13372.
[] [PMID: 26303320]
Nasser, M.I.; Masood, M.; Wei, W.; Li, X.; Zhou, Y.; Liu, B.; Li, J.; Li, X. Cordycepin induces apoptosis in SGC7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS. Int. J. Oncol., 2017, 50(3), 911-919.
[] [PMID: 28197639]
Baik, J.S.; Mun, S.W.; Kim, K.S.; Park, S.J.; Yoon, H.K.; Kim, D.H.; Park, M.K.; Kim, C.H.; Lee, Y.C. Apoptotic effects of cordycepin through the extrinsic pathway and p38 MAPK activation in human glioblastoma U87MG cells. J. Microbiol. Biotechnol., 2016, 26(2), 309-314.
[] [PMID: 26597532]
Chang, W.; Lim, S.; Song, H.; Song, B.W.; Kim, H.J.; Cha, M.J.; Sung, J.M.; Kim, T.W.; Hwang, K.C. Cordycepin inhibits vascular smooth muscle cell proliferation. Eur. J. Pharmacol., 2008, 597(1-3), 64-69.
[] [PMID: 18782572]
Lee, Y.R.; Noh, E.M.; Jeong, E.Y.; Yun, S.K.; Jeong, Y.J.; Kim, J.H.; Kwon, K.B.; Kim, B.S.; Lee, S.H.; Park, C.S.; Kim, J.S. Cordycepin inhibits UVB-induced matrix metalloproteinase expression by suppressing the NF-kappaB pathway in human dermal fibroblasts. Exp. Mol. Med., 2009, 41(8), 548-554.
[] [PMID: 19381070]
Lee, E.J.; Kim, W.J.; Moon, S.K. Cordycepin suppresses TNF-alpha-induced invasion, migration and matrix metalloproteinase-9 expression in human bladder cancer cells. Phytother. Res., 2010, 24(12), 1755-1761.
[] [PMID: 20564512]
Noh, E.M.; Youn, H.J.; Jung, S.H.; Han, J.H.; Jeong, Y.J.; Chung, E.Y.; Jung, J.Y.; Kim, B.S.; Lee, S.H.; Lee, Y.R.; Kim, J.S. Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells. Int. J. Mol. Med., 2010, 25(2), 255-260.
[PMID: 20043135]
Jeong, J.W.; Jin, C.Y.; Park, C.; Han, M.H.; Kim, G.Y.; Moon, S.K.; Kim, C.G.; Jeong, Y.K.; Kim, W.J.; Lee, J.D.; Choi, Y.H. Inhibition of migration and invasion of LNCaP human prostate carcinoma cells by cordycepin through inactivation of Akt. Int. J. Oncol., 2012, 40(5), 1697-1704.
[PMID: 22246470]
Lee, H.J.; Burger, P.; Vogel, M.; Friese, K.; Brüning, A. The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells. Invest. New Drugs, 2012, 30(5), 1917-1925.
[] [PMID: 22821173]
Choi, S.; Lim, M.H.; Kim, K.M.; Jeon, B.H.; Song, W.O.; Kim, T.W. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor. Toxicol. Appl. Pharmacol., 2011, 257(2), 165-173.
[] [PMID: 21933677]
Noh, E.M.; Kim, J.S.; Hur, H.; Park, B.H.; Song, E.K.; Han, M.K.; Kwon, K.B.; Yoo, W.H.; Shim, I.K.; Lee, S.J.; Youn, H.J.; Lee, Y.R. Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts. Rheumatology (Oxford), 2009, 48(1), 45-48.
[] [PMID: 19056796]
Ren, Z.; Cui, J.; Huo, Z.; Xue, J.; Cui, H.; Luo, B.; Jiang, L.; Yang, R. Cordycepin suppresses TNF-α-induced NF-κB activation by reducing p65 transcriptional activity, inhibiting IκBα phosphorylation, and blocking IKKγ ubiquitination. Int. Immunopharmacol., 2012, 14(4), 698-703.
[] [PMID: 23102662]
Ko, B.S.; Lu, Y.J.; Yao, W.L.; Liu, T.A.; Tzean, S.S.; Shen, T.L.; Liou, J.Y. Cordycepin regulates GSK-3β/β-catenin signaling in human leukemia cells. PLoS One, 2013, 8(9)e76320
[] [PMID: 24086728]
Wu, W.D.; Hu, Z.M.; Shang, M.J.; Zhao, D.J.; Zhang, C.W.; Hong, D.F.; Huang, D.S. Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1α through regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells. Int. J. Mol. Sci., 2014, 15(7), 12778-12790.
[] [PMID: 25046749]
Tian, X.; Li, Y.; Shen, Y.; Li, Q.; Wang, Q.; Feng, L. Apoptosis and inhibition of proliferation of cancer cells induced by cordycepin. Oncol. Lett., 2015, 10(2), 595-599.
[] [PMID: 26622539]
Yang, C.; Zhao, L.; Yuan, W.; Wen, J. Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN phosphatase. Biomed. Res. (Aligarh), 2017, 38(5), 313-320.
[] [PMID: 29070781]
Lee, H.H.; Kim, S.O.; Kim, G.Y.; Moon, S.K.; Kim, W.J.; Jeong, Y.K.; Yoo, Y.H.; Choi, Y.H. Involvement of autophagy in cordycepin-induced apoptosis in human prostate carcinoma LNCaP cells. Environ. Toxicol. Pharmacol., 2014, 38(1), 239-250.
[] [PMID: 24973666]
Yu, X.; Ling, J.; Liu, X.; Guo, S.; Lin, Y.; Liu, X.; Su, L. Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells. Oncotarget, 2017, 8(4), 6691-6699.
[] [PMID: 28035061]
Chaicharoenaudomrung, N.; Jaroonwitchawan, T.; Noisa, P. Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy. Toxicol. In Vitro, 2018, 46, 113-121.
[] [PMID: 28987792]
Chen, X.; Wang, Y.; Liu, J.; Xu, P.; Zhang, X.M.; Tian, Y.Y.; Xue, Y.M.; Gao, X.Y.; Liu, Y.; Wang, J.H. Synergistic effect of HMGB1 knockdown and cordycepin in the K562 human chronic myeloid leukemia cell line. Mol. Med. Rep., 2015, 12(3), 4462-4468.
[] [PMID: 26081986]
Yao, W.L.; Ko, B.S.; Liu, T.A.; Liang, S.M.; Liu, C.C.; Lu, Y.J.; Tzean, S.S.; Shen, T.L.; Liou, J.Y. Cordycepin suppresses integrin/FAK signaling and epithelial-mesenchymal transition in hepatocellular carcinoma. Anticancer. Agents Med. Chem., 2014, 14(1), 29-34.
[] [PMID: 23855336]
Khan, M.A.; Chen, H.C.; Zhang, D.; Fu, J. Twist: a molecular target in cancer therapeutics. Tumour Biol., 2013, 34(5), 2497-2506.
[] [PMID: 23873099]
Tania, M.; Khan, M.A.; Fu, J. Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer. Tumour Biol., 2014, 35(8), 7335-7342.
[] [PMID: 24880591]
Zhang, P.; Huang, C.; Fu, C.; Tian, Y.; Hu, Y.; Wang, B.; Strasner, A.; Song, Y.; Song, E. Cordycepin (3′-deoxyadenosine) suppressed HMGA2, Twist1 and ZEB1-dependent melanoma invasion and metastasis by targeting miR-33b. Oncotarget, 2015, 6(12), 9834-9853.
[] [PMID: 25868853]
Wang, C.W.; Hsu, W.H.; Tai, C.J. Antimetastatic effects of cordycepin mediated by the inhibition of mitochondrial activity and estrogen-related receptor α in human ovarian carcinoma cells. Oncotarget, 2017, 8(2), 3049-3058.
[] [PMID: 27966445]
Hueng, D.Y.; Hsieh, C.H.; Cheng, Y.C.; Tsai, W.C.; Chen, Y. Cordycepin inhibits migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation. J. Nutr. Biochem., 2017, 41, 109-116.
[] [PMID: 28068557]
Tao, X.; Ning, Y.; Zhao, X.; Pan, T. The effects of cordycepin on the cell proliferation, migration and apoptosis in human lung cancer cell lines A549 and NCI-H460. J. Pharm. Pharmacol., 2016, 68(7), 901-911.
[] [PMID: 27138740]
Wang, C.W.; Lee, B.H.; Tai, C.J. The inhibition of cordycepin on cancer stemness in TGF-beta induced chemo-resistant ovarian cancer cell. Oncotarget, 2017, 8(67), 111912-111921.
[] [PMID: 29340100]
Jagger, D.V.; Kredich, N.M.; Guarino, A.J. Inhibition of Ehrlich mouse ascites tumor growth by cordycepin. Cancer Res., 1961, 21, 216-220.
[PMID: 13789180]
Yoshikawa, N.; Nakamura, K.; Yamaguchi, Y.; Kagota, S.; Shinozuka, K.; Kunitomo, M. Antitumour activity of cordycepin in mice. Clin. Exp. Pharmacol. Physiol., 2004, 31(Suppl. 2), S51-S53.
[] [PMID: 15649290]
Nakamura, K.; Konoha, K.; Yoshikawa, N.; Yamaguchi, Y.; Kagota, S.; Shinozuka, K.; Kunitomo, M. Effect of cordycepin (3′-deoxyadenosine) on hematogenic lung metastatic model mice. In Vivo, 2005, 19(1), 137-141.
[PMID: 15796166]
Yoshikawa, N.; Kunitomo, M.; Kagota, S.; Shinozuka, K.; Nakamura, K. Inhibitory effect of cordycepin on hematogenic metastasis of B16-F1 mouse melanoma cells accelerated by adenosine-5′-diphosphate. Anticancer Res., 2009, 29(10), 3857-3860.
[PMID: 19846919]
Sato, A.; Yoshikawa, N.; Kubo, E.; Kakuda, M.; Nishiuchi, A.; Kimoto, Y.; Takahashi, Y.; Kagota, S.; Shinozuka, K.; Nakamura, K. Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0 mouse melanoma cells. In Vivo, 2013, 27(6), 729-732.
[PMID: 24292575]
Su, N.W.; Wu, S.H.; Chi, C.W.; Liu, C.J.; Tsai, T.H.; Chen, Y.J. Metronomic cordycepin therapy prolongs survival of oral cancer-bearing mice and inhibits epithelial-mesenchymal transition. Molecules, 2017, 22(4) E629
[] [PMID: 28406456]
Foss, F.M. Combination therapy with purine nucleoside analogs. Oncology (Williston Park), 2000, 14(6)(Suppl. 2), 31-35.
[PMID: 10887642]
Tsai, Y.J.; Lin, L.C.; Tsai, T.H. Pharmacokinetics of adenosine and cordycepin, a bioactive constituent of Cordyceps sinensis in rat. J. Agric. Food Chem., 2010, 58(8), 4638-4643.
[] [PMID: 20302371]
Wehbe-Janek, H.; Shi, Q.; Kearney, C.M. Cordycepin/Hydroxyurea synergy allows low dosage efficacy of cordycepin in MOLT-4 leukemia cells. Anticancer Res., 2007, 27(5A), 3143-3146.
[PMID: 17970055]
Li, G.; Nakagome, I.; Hirono, S.; Itoh, T.; Fujiwara, R. Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances. Pharmacol. Res. Perspect., 2015, 3(2) e00121
[] [PMID: 26038697]
Agarwal, R.P. Deoxycoformycin toxicity in mice after long-term treatment. Cancer Chemother. Pharmacol., 1980, 5(2), 83-87.
[] [PMID: 6970629]
Rodman, L.E.; Farnell, D.R.; Coyne, J.M.; Allan, P.W.; Hill, D.L.; Duncan, K.L.; Tomaszewski, J.E.; Smith, A.C.; Page, J.G. Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2′-deoxycoformycin in beagle dogs. Toxicol. Appl. Pharmacol., 1997, 147(1), 39-45.
[] [PMID: 9356305]
Dalla Rosa, L.; Da Silva, A.S.; Oliveira, C.B.; Gressler, L.T.; Arnold, C.B.; Baldissera, M.D.; Sagrillo, M.; Sangoi, M.; Moresco, R.; Mendes, R.E.; Weiss, P.E.; Miletti, L.C.; Monteiro, S.G. Dose finding of 3'deoxyadenosine and deoxycoformycin for the treatment of Trypanosoma evansi infection: An effective and nontoxic dose. Microb. Pathog., 2015, 85, 21-28.
[] [PMID: 26025154]
Rottenberg, M.E.; Masocha, W.; Ferella, M.; Petitto-Assis, F.; Goto, H.; Kristensson, K.; McCaffrey, R.; Wigzell, H. Treatment of African trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model. J. Infect. Dis., 2005, 192(9), 1658-1665.
[] [PMID: 16206083]
Aramwit, P.; Porasuphatana, S.; Srichana, T.; Nakpheng, T. Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity. Nanoscale Res. Lett., 2015, 10, 152.
[] [PMID: 25883541]
Wu, P.K.; Tao, Z.; Ouyang, Z.; Cao, J.Y.; Geng, D.; Liu, J.; Wang, C.M. The anti-tumor effects of cordycepin-loaded liposomes on the growth of hepatoma 22 tumors in mice and human hepatoma BEL-7402 cells in culture. Drug Dev. Ind. Pharm., 2016, 42(9), 1424-1433.
[] [PMID: 26984179]
Bi, Y.E.; Zhou, Y.; Wang, M.; Li, L.; Lee, R.J.; Xie, J.; Teng, L. Targeted delivery of cordycepin to liver cancer cells using transferrin-conjugated liposomes. Anticancer Res., 2017, 37(9), 5207-5214.
[PMID: 28870956]
Cho, S.H.; Kang, I.C. The inhibitory effect of Cordycepin on the proliferation of cisplatin-resistant A549 lung cancer cells. Biochem. Biophys. Res. Commun., 2018, 498(3), 431-436.
[] [PMID: 29496448]

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