Allicin induces apoptosis through activation of both intrinsic and extrinsic pathways in glioma cells

Li,Chenlong; Jing,Hanguang; Ma,Guangtao; Liang,Peng

doi:10.3892/mmr.2018.8552

Allicin induces apoptosis through activation of both intrinsic and extrinsic pathways in glioma cells

Authors:
- Chenlong Li
- Hanguang Jing
- Guangtao Ma
- Peng Liang
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Affiliations: Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150086, P.R. China, Basic Theory of Chinese Medicine, Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China, Department of Neurosurgery, Daqing Oil Field General Hospital, Daqing, Heilongjiang 163000, P.R. China
Published online on: February 2, 2018 https://doi.org/10.3892/mmr.2018.8552
Pages: 5976-5981

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Abstract

Allicin is an extract purified from Allium sativum (garlic), and previous research has indicated that Allicin has an inhibitory effect on many kinds of tumor cells. The aim of the present study was to explore the anticancer activity of Allicin on human glioma cells and investigate the underlying mechanism. MTT and colony-formation assays were performed to detect glioma cell proliferation, and explore the effect of Allicin at various doses and time-points. The apoptosis of glioma cells was measured by fluorescence microscopy with Hoechst 33258 staining, and then flow cytometry was used to analyzed changes in glioma cell apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to detect the effect of Allicin on the expression levels of Fas/Fas ligand (FasL), caspase‑3, B‑cell lymphoma 2 and Bcl‑2‑associated X protein. Allicin suppressed the proliferation and colony formation ability of U251 cells in a dose‑ and time‑dependent manner. A cytotoxic effect of Allicin was observed in glioma cells in a dose‑dependent manner. Changes in nuclear morphology were observed in U251 cells with Hoechst 33258 staining. The activity of caspases were significantly elevated and Fas/FasL expression levels were increased following treatment with Allicin, at both the mRNA and protein level. These results demonstrated that Allicin suppresses proliferation and induces glioma cell apoptosis in vitro. Both intrinsic mitochondrial and extrinsic Fas/FasL‑mediated pathways react in glioma cell after treating with Allicin, which then activate major apoptotic cascades. These results implicate Allicin as a novel antitumor agent in treating glioma.

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1	Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P and Ellison DW: The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 131:803–820. 2016. View Article : Google Scholar : PubMed/NCBI
2	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
3	Bush NA, Chang SM and Berger MS: Current and future strategies for treatment of glioma. Neurosurg Rev. 14:1–14. 2017. View Article : Google Scholar
4	Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ: Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin. 60:166–193. 2010. View Article : Google Scholar : PubMed/NCBI
5	Zhou H, Qu Z, Mossine VV, Nknolise DL, Li J, Chen Z, Cheng J, Greenlief CM, Mawhinney TP, Brown PN, et al: Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells. PLoS One. 9:e1135312014. View Article : Google Scholar : PubMed/NCBI
6	Lissiman E, Bhasale AL and Cohen M: Garlic for the common cold. Cochrane Database Syst Rev: CD006206. 2009. View Article : Google Scholar
7	Chu YL, Ho CT, Chung JG, Rajasekaran R and Sheen LY: Allicin induces p53-mediated autophagy in HepG2 human liver cancer cells. J Agric Food Chem. 60:8363–8371. 2012. View Article : Google Scholar : PubMed/NCBI
8	Chu YL, Ho CT, Chung JG, Raghu R, Lo YC and Sheen LY: Allicin induces anti-human liver cancer cells through the p53 gene modulating apoptosis and autophagy. J Agric Food Chem. 61:9839–9848. 2013. View Article : Google Scholar : PubMed/NCBI
9	Zou X, Liang J, Sun J, Hu X, Lei L, Wu D and Liu L: Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway. J Pharmacol Sci. 131:233–240. 2016. View Article : Google Scholar : PubMed/NCBI
10	Fuchs Y and Steller H: Programmed cell death in animal development and disease. Cell. 147:742–758. 2011. View Article : Google Scholar : PubMed/NCBI
11	Wang W, Zheng Z, Yu W, Lin H, Cui B and Cao F: Polymorphisms of the FAS and FASL genes and risk of breast cancer. Oncol Lett. 3:625–628. 2012. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Lapinski TW, Jaroszewicz J and Wiercinska-Drapalo A: Concentrations of soluble Fas and soluble Fas ligand as indicators of programmed cell death among patients coinfected with human immunodeficiency virus and hepatitis C virus. Viral Immunol. 19:570–575. 2006. View Article : Google Scholar : PubMed/NCBI
14	Shea A, Harish V, Afzal Z, Chijioke J, Kedir H, Dusmatova S, Roy A, Ramalinga M, Harris B, Blancato J, et al: MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics. Cancer Med. 5:1917–1946. 2016. View Article : Google Scholar : PubMed/NCBI
15	Dvořáková M, Weingartová I, Nevoral J, Němeček D and Krejčová T: Garlic sulfur compounds suppress cancerogenesis and oxidative stress: A review. Scientia Agriculturae Bohemica. 46:65–72. 2015. View Article : Google Scholar
16	Wang W, Du Z, Nimiya Y, Sukamtoh E, Kim D and Zhang G: Allicin inhibits lymphangiogenesis through suppressing activation of vascular endothelial growth factor (VEGF) receptor. J Nutr Biochem. 29:83–89. 2016. View Article : Google Scholar : PubMed/NCBI
17	Oommen S, Anto RJ, Srinivas G and Karunagaran D: Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur J Pharmacol. 485:97–103. 2004. View Article : Google Scholar : PubMed/NCBI
18	Hebert DN, Lamriben L, Powers ET and Kelly JW: The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis. Nat Chem Biol. 10:902–910. 2014. View Article : Google Scholar : PubMed/NCBI
19	Li CL, Chang L, Guo L, Zhao D, Liu HB, Wang QS, Zhang P, Du WZ, Liu X, Zhang HT, et al: β-Elemene induces caspase-dependent apoptosis in human glioma cells in vitro through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2. Asian Pac J Cancer Prev. 15:10407–10412. 2014. View Article : Google Scholar : PubMed/NCBI
20	Zhang W, Ha M, Gong Y, Xu Y, Dong N and Yuan Y: Allicin induces apoptosis in gastric cancer cells through activation of both extrinsic and intrinsic pathways. Oncol Rep. 24:1585–1592. 2010.PubMed/NCBI
21	Liu Z, Ding Y, Ye N, Wild C, Chen H and Zhou J: Direct activation of Bax protein for cancer therapy. Med Res Rev. 36:313–341. 2016. View Article : Google Scholar : PubMed/NCBI
22	Jiang X and Wang X: Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J Biol Chem. 275:31199–31203. 2000. View Article : Google Scholar : PubMed/NCBI
23	Du X, Zhao YP, Zhang TP, Zhou L, Chen G, Wang TX, You L and Shu H: Alteration of the intrinsic apoptosis pathway is involved in Notch-induced chemoresistance to gemcitabine in pancreatic cancer. Arch Med Res. 45:15–20. 2014. View Article : Google Scholar : PubMed/NCBI