Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells Retraction in /10.3892/ol.2023.14173

Maimaitili,Aisha; Shu,Zunhua; Cheng,Xiaojiang; Kaheerman,Kadeer; Sikandeer,Alifu; Li,Weimin

doi:10.3892/ol.2016.5474

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

Retraction in: /10.3892/ol.2023.14173

Authors:
- Aisha Maimaitili
- Zunhua Shu
- Xiaojiang Cheng
- Kadeer Kaheerman
- Alifu Sikandeer
- Weimin Li
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830054, P.R. China, Department of Medical Affairs, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130021, P.R. China
Published online on: December 8, 2016 https://doi.org/10.3892/ol.2016.5474
Pages: 1007-1013

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Abstract

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose‑dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60‑75% reduction in colony formation compared with vehicle‑treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G0/G1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin‑dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro‑apoptotic BCL2‑associated X protein. Furthermore, arctigenin‑induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD‑FMK, a caspase‑3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G0/G1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

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1	Yu X, Zhang W, Ning Q and Luo X: MicroRNA-34a inhibits human brain glioma cell growth by down-regulation of Notch1. J Huazhong Univ Sci Technolog Med Sci. 32:370–374. 2012. View Article : Google Scholar : PubMed/NCBI
2	Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M and Fisher J: NABTT CNS and Consortium: Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 16:2443–2449. 2010. View Article : Google Scholar : PubMed/NCBI
3	Vermeulen K, Van Bockstaele DR and Berneman ZN: The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36:131–149. 2003. View Article : Google Scholar : PubMed/NCBI
4	Borgne A and Golsteyn RM: The role of cyclin-dependent kinases in apoptosis. Prog Cell Cycle Res. 5:453–459. 2003.PubMed/NCBI
5	Ruijtenberg S and van den Heuvel S: Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. Cell Cycle. 15:196–212. 2016. View Article : Google Scholar : PubMed/NCBI
6	Indovina P, Pentimalli F, Casini N, Vocca I and Giordano A: RB1 dual role in proliferation and apoptosis: Cell fate control and implications for cancer therapy. Oncotarget. 6:17873–17890. 2015. View Article : Google Scholar : PubMed/NCBI
7	Kudou N, Taniguchi A, Sugimoto K, Matsuya Y, Kawasaki M, Toyooka N, Miyoshi C, Awale S, Dibwe DF, Esumi H, et al: Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy. Eur J Med Chem. 60:76–88. 2012. View Article : Google Scholar : PubMed/NCBI
8	Jeong JB, Hong SC, Jeong HJ and Koo JS: Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells. Int Immunopharmacol. 11:1573–1577. 2011. View Article : Google Scholar : PubMed/NCBI
9	Hsieh CJ, Kuo PL, Hsu YC, Huang YF, Tsai EM and Hsu YL: Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation. Free Radic Biol Med. 67:159–170. 2014. View Article : Google Scholar : PubMed/NCBI
10	Huang K, Li LA, Meng YG, You YQ, Fu XY and Song L: Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling. Basic Clin Pharmacol Toxicol. 115:507–511. 2014. View Article : Google Scholar : PubMed/NCBI
11	Xiao J, Liu L, Zhong Z, Xiao C and Zhang J: Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression. Oncol Rep. 33:2815–2820. 2015.PubMed/NCBI
12	Çiftçi GA, Işcan A and Kutlu M: Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines. Cytotechnology. 67:893–904. 2015. View Article : Google Scholar : PubMed/NCBI
13	Li W, Qi Z, Wei Z, Liu S, Wang P, Chen Y and Zhao Y: Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation. Mol Med Rep. 12:2735–2740. 2015.PubMed/NCBI
14	Yang S, Ma J, Xiao J, Lv X, Li X, Yang H, Liu Y, Feng S and Zhang Y: Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis. Anat Rec (Hoboken). 295:1260–1266. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ouyang Q, Xu L, Cui H, Xu M and Yi L: MicroRNAs and cell cycle of malignant glioma. Int J Neurosci. 126:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
16	Changa YC, Choua FP, Huanga HP, Hsub JD and Wang CJ: Inhibition of cell cycle progression by penta-acetyl geniposide in rat C6 glioma cells. Toxicol Appl Pharmacol. 198:11–20. 2004. View Article : Google Scholar : PubMed/NCBI
17	Gomez-Manzano C, Fueyo J, Kyritsis AP, McDonnell TJ, Steck PA, Levin VA and Yung WK: Characterization of p53 and p21 functional interactions in glioma cells en route to apoptosis. J Natl Cancer Inst. 89:1036–1044. 1997. View Article : Google Scholar : PubMed/NCBI
18	Igata M, Motoshima H, Tsuruzoe K, Kojima K, Matsumura T, Kondo T, Taguchi T, Nakamaru K, Yano M, Kukidome D, et al: Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res. 97:837–844. 2005. View Article : Google Scholar : PubMed/NCBI
19	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
20	Yao X, Zhu F, Zhao Z, Liu C, Luo L and Yin Z: Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway. J Cell Biochem. 112:2837–2849. 2011. View Article : Google Scholar : PubMed/NCBI