Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells

Li,Yifan; Li,Rong; Zhu,Shenglang; Zhou,Ruyun; Wang,Lei; Du,Jihui; Wang,Yong; Zhou,Bei; Mai,Liwen

doi:10.3892/ol.2015.3066

Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells

Authors:
- Yifan Li
- Rong Li
- Shenglang Zhu
- Ruyun Zhou
- Lei Wang
- Jihui Du
- Yong Wang
- Bei Zhou
- Liwen Mai
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Affiliations: Central Laboratory, Affiliated Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China, Department of Nephrology, Affiliated Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China, Department of Chinese Traditional Medicine Rheumatology, Affiliated Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China, Department of Gastroenterology, Affiliated Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China
Published online on: March 23, 2015 https://doi.org/10.3892/ol.2015.3066
Pages: 2541-2547
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cordycepin, also termed 3'-deoxyadenosine, is a derivative of the nucleoside adenosine that represents a potential novel class of anticancer drugs targeting the 3' untranslated region of RNAs. Cordycepin has been reported to induce apoptosis in certain cancer cell lines, but the effects of cordycepin on human neuroblastoma cells have not been studied. In the present study, an MTT assay revealed that cordycepin inhibits the viability of neuroblastoma SK‑N‑SH and BE(2)‑M17 cells in a dose‑dependent manner. In addition, cordycepin increases the early‑apoptotic cell population of SK‑N‑SH cells, as determined by fluorescence‑activated cell sorting analysis. The induction of apoptosis in neuroblastoma cells by cordycepin was further confirmed by western blotting, which revealed cleavage of caspase‑3 and poly(adenosine diphosphate‑ribose) polymerase 1 in the SK‑N‑SH and BE(2)‑M17 cells. Cordycepin also induced the formation of a punctate pattern of light‑chain 3 (LC3)‑associated green fluorescence in the SK‑N‑SH cells transfected with a pEGFP‑LC3 vector. Furthermore, western blotting revealed cleavage of LC3 A/B in cordycepin‑treated neuroblastoma SK‑N‑SH cells. Taken together, the results indicate that cordycepin significantly increases apoptosis and autophagy in neuroblastoma cells, and may therefore be a drug candidate for neuroblastoma therapy, but requires additional evaluation.

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1	Gurney JG, Ross JA, Wall DA, Bleyer WA, Severson RK and Robison LL: Infant Cancer in the U.S.: histology-specific incidence and trends, 1973 to 1992. J Pediatr Hematol Oncol. 19:428–432. 1997. View Article : Google Scholar : PubMed/NCBI
2	Spix C, Pastore G, Sankila R, Stiller CA and Steliarova-Foucher E: Neuroblastoma incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer. 42:2081–2091. 2006. View Article : Google Scholar : PubMed/NCBI
3	Brodeur GM: Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 3:203–216. 2003. View Article : Google Scholar : PubMed/NCBI
4	Maris JM, Hogarty MD, Bagatell R and Cohn SL: Neuroblastoma. Lancet. 369:2106–2120. 2007. View Article : Google Scholar : PubMed/NCBI
5	Brodeur GM, Pritchard J, Berthold F, et al: Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 11:1466–1477. 1993.PubMed/NCBI
6	National Cancer Society: Neuroblastoma risk groups. http://www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-risk-groupsAccessed. February 16–2015.
7	Al-Salem AH: An Illustrated Guide to Pediatric Surgery. Springer International Publishing AG. Switzerland: 2014. View Article : Google Scholar
8	D'Angio GJ, Evans AE and Koop CE: Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet. 1:1046–1049. 1971. View Article : Google Scholar : PubMed/NCBI
9	Brodeur GM, Seeger RC, Barrett A, et al: International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol. 6:1874–1881. 1988.PubMed/NCBI
10	Diede SJ: Spontaneous regression of metastatic cancer: learning from neuroblastoma. Nat Rev Cancer. 14:71–72. 2014. View Article : Google Scholar : PubMed/NCBI
11	Hallett A and Traunecker H: A review and update on neuroblastoma. Paediatrics and Child Health. 22:103–107. 2012. View Article : Google Scholar
12	Cheung NK and Dyer MA: Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 13:397–411. 2013. View Article : Google Scholar : PubMed/NCBI
13	Maris JM: Recent advances in neuroblastoma. N Engl J Med. 362:2202–2211. 2010. View Article : Google Scholar : PubMed/NCBI
14	Matthay KK, Villablanca JG, Seeger RC, et al: Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med. 341:1165–1173. 1999. View Article : Google Scholar : PubMed/NCBI
15	Kondrashov A, Meijer HA, Barthet-Barateig A, et al: Inhibition of polyadenylation reduces inflammatory gene induction. RNA. 18:2236–2250. 2012. View Article : Google Scholar : PubMed/NCBI
16	Tuli HS, Sharma AK, Sandhu SS and Kashyap D: Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci. 93:863–869. 2013. View Article : Google Scholar : PubMed/NCBI
17	Siev M, Weinberg R and Penman S: The selective interruption of nucleolar RNA synthesis in HeLa cells by cordycepin. J Cell Biol. 41:510–520. 1969. View Article : Google Scholar : PubMed/NCBI
18	Hollerer I, Grund K, Hentze MW and Kulozik AE: mRNA 3′end processing: A tale of the tail reaches the clinic. EMBO Mol Med. 6:16–26. 2014. View Article : Google Scholar : PubMed/NCBI
19	Choi S, Lim MH, Kim KM, Jeon BH, Song WO and Kim TW: Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor. Toxicol Appl Pharmacol. 257:165–173. 2011. View Article : Google Scholar : PubMed/NCBI
20	Lee SY, Debnath T, Kim SK and Lim BO: Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29. Food Chem Toxicol. 60:439–447. 2013. View Article : Google Scholar : PubMed/NCBI
21	Chen YH, Hao LJ, Hung CP, Chen JW, Leu SF and Huang BM: Apoptotic effect of cisplatin and cordycepin on OC3 human oral cancer cells. Chin J Integr Med. 20:624–632. 2014. View Article : Google Scholar : PubMed/NCBI
22	Jen CY, Lin CY, Huang BM and Leu SF: Cordycepin Induced Ma-10 Mouse Leydig Tumor Cell Apoptosis through Caspase-9 Pathway. Evid Based Complement Alternat Med. 2011.9845372011.PubMed/NCBI
23	Wu WC, Hsiao JR, Lian YR, Lin CY and Huang BM: The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother Pharmacol. 60:103–111. 2007. View Article : Google Scholar : PubMed/NCBI
24	National Cancer Institute: Chemotherapy with cordycepin plus pentostatin in treating patients with refractory acute lymphocytic or chronic myelogenous leukemia. http://www.cancer.gov/clinicaltrials/search/view?cdrid=65572&version=healthprofessionalAccessed. June 10–2014.
25	Huang TT, Chong KY, Ojcius DM, et al: Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes. Sci Rep. 3:13742013. View Article : Google Scholar : PubMed/NCBI
26	Li C, Li Z, Fan M, et al: The composition of Hirsutella sinensis, anamorph of Cordyceps sinensis. J Food Compost Anal. 19:800–805. 2006. View Article : Google Scholar
27	Szemes M, Dallosso AR, Melegh Z, et al: Control of epigenetic states by WT1 via regulation of de novo DNA methyltransferase 3A. Hum Mol Genet. 22:74–83. 2013. View Article : Google Scholar : PubMed/NCBI
28	Kabeya Y, Mizushima N, Ueno T, et al: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI
29	Elmore S: Apoptosis: a review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
30	Oh JY, Baek YM, Kim SW, et al: Apoptosis of human hepatocarcinoma (HepG2) and neuroblastoma (SKN-SH) cells induced by polysaccharides-peptide complexes produced by submerged mycelial culture of an entomopathogenic fungus Cordyceps sphecocephala. J Microbiol Biotechnol. 18:512–519. 2008.PubMed/NCBI
31	Yang CH, Kao YH, Huang KS, Wang CY and Lin LW: Cordyceps militaris and mycelial fermentation induced apoptosis and autophagy of human glioblastoma cells. Cell Death Dis. 3:e4312012. View Article : Google Scholar : PubMed/NCBI
32	Wu YT, Tan HL, Shui G, et al: Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 285:10850–10861. 2010. View Article : Google Scholar : PubMed/NCBI
33	Boya P, González-Polo RA, Casares N, et al: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol. 25:1025–1040. 2005. View Article : Google Scholar : PubMed/NCBI