Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro

Zhou,Guo-Sheng; Song,Lai-Jun; Yang,Bo

doi:10.3892/mmr.2012.1218

Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro

Authors:
- Guo-Sheng Zhou
- Lai-Jun Song
- Bo Yang
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Affiliations: Neurosurgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: December 3, 2012 https://doi.org/10.3892/mmr.2012.1218
Pages: 531-536

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Abstract

Isoliquiritigenin (ISL), a member of the flavonoids, has been demonstrated to possess antitumor activity in various cancer cell lines in vitro and in vivo. In this study, we investigated the antitumor effects of ISL on U87 glioma cells in vitro. As determined by MTT assay, ISL inhibited the proliferation of U87 cells in a time-dependent and dose-dependent manner. The results of fluorescence-activated cell sorting (FACS) analysis suggested that ISL induced the apoptosis of the U87 cells and blocked cell cycle progression at the S and G2/M phases. Moreover, it was identified that ISL induced the apoptosis of the U87 cells in a caspase-dependent manner. Although treatment with the pan-caspase inhibitor Z-VAD-FMK efficiently blocked the ISL-induced caspase activation, it did not eliminate the ISL-induced cell death. Further examination using western blot analysis revealed that ISL upregulated p21/WAF1 and p27. These results indicate that cell cycle arrest and the caspase-mediated apoptosis pathway may participate in the antiproliferative activity of ISL in U87 cells by regulating the expression of specific molecules.

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1	Lima FR, Kahn SA, Soletti RC, Biasoli D, Alves T, da Fonseca AC, et al: Glioblastoma: Therapeutic challenges, what lies ahead. Biochim Biophys Acta. 1826:338–349. 2012.PubMed/NCBI
2	Ma X, Lv Y, Liu J, Wang D, Huang Q, Wang X, Li G, Xu S and Li X: Survival analysis of 205 patients with glioblastoma multiforme: clinical characteristics, treatment and prognosis in China. J Clin Neurosci. 16:1595–1598. 2009. View Article : Google Scholar : PubMed/NCBI
3	Davis ME and Stoiber AM: Glioblastoma multiforme: enhancing survival and quality of life. Clin J Oncol Nurs. 15:291–297. 2011. View Article : Google Scholar : PubMed/NCBI
4	Lin H, Liu J and Zhang Y: Developments in cancer prevention and treatment using traditional Chinese medicine. Front Med. 5:127–133. 2011. View Article : Google Scholar : PubMed/NCBI
5	Efferth T, Li PC, Konkimalla VS and Kaina B: From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 13:353–361. 2007. View Article : Google Scholar : PubMed/NCBI
6	Wang S, Wu X, Tan M, Gong J, Tan W, Bian B, Chen M and Wang Y: Fighting fire with fire: poisonous Chinese herbal medicine for cancer therapy. J Ethnopharmacol. 140:33–45. 2012. View Article : Google Scholar : PubMed/NCBI
7	Kandaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT and Lee MT: The antitumor activities of flavonoids. In Vivo. 19:895–909. 2005.PubMed/NCBI
8	Weng CJ and Yen GC: Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev. 31:323–351. 2012. View Article : Google Scholar : PubMed/NCBI
9	Lee CK, Son SH, Park KK, Park JH, Lim SS and Chung WY: Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma. J Pharmacol Sci. 106:444–451. 2008. View Article : Google Scholar
10	Orlikova B, Schnekenburger M, Zloh M, Golais F, Diederich M and Tasdemir D: Natural chalcones as dual inhibitors of HDACs and NF-κB. Oncol Rep. 28:797–805. 2012.PubMed/NCBI
11	Lee YM, Jeong GS, Lim HD, An RB, Kim YC and Kim EC: Isoliquiritigenin 2-methyl ether induces growth inhibition and apoptosis in oral cancer cells via heme oxygenase-1. Toxicol In Vitro. 24:776–782. 2010. View Article : Google Scholar : PubMed/NCBI
12	Auyeung KK and Ko JK: Novel herbal flavonoids promote apoptosis but differentially induce cell cycle arrest in human colon cancer cell. Invest New Drugs. 28:1–13. 2010. View Article : Google Scholar : PubMed/NCBI
13	Lau GT, Ye L and Leung LK: The licorice flavonoid isoliquiritigenin suppresses phorbol ester-induced cyclooxygenase-2 expression in the non-tumorigenic MCF-10A breast cell line. Planta Med. 76:780–785. 2010. View Article : Google Scholar : PubMed/NCBI
14	Ye L, Gho WM, Chan FL, Chen S and Leung LK: Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase. Int J Cancer. 124:1028–1036. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ma J, Fu NY, Pang DB, Wu WY and Xu AL: Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Med. 67:754–777. 2001. View Article : Google Scholar : PubMed/NCBI
16	Zhang X, Yeung ED, Wang J, Panzhinskiy EE, Tong C, Li W and Li J: Isoliquiritigenin, a natural anti-oxidant, selectively inhibits the proliferation of prostate cancer cells. Clin Exp Pharmacol Physiol. 37:841–847. 2010.PubMed/NCBI
17	Iwashita K, Kobori M, Yamaki K and Tsushida T: Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci Biotechnol Biochem. 64:1813–1820. 2000. View Article : Google Scholar : PubMed/NCBI
18	Hsu YL, Kuo PL, Chiang LC and Lin CC: Isoliquiritigenin inhibits the proliferation and induces the apoptosis of human non-small cell lung cancer A549 cells. Clin Exp Pharmacol Physiol. 31:414–418. 2004. View Article : Google Scholar : PubMed/NCBI
19	Li T, Satomi Y, Kotoh D, Shimada J, Baba M, Okuyama T, Nishino H and Kitamura N: Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett. 207:27–35. 2004. View Article : Google Scholar : PubMed/NCBI
20	Lee YM, Lim do Y, Choi HJ, Jung JL, Chung WY and Park JH: Induction of cell cycle arrest in prostate cancer cells by the dietary compound isoliquiritigenin. J Med Food. 12:8–14. 2009. View Article : Google Scholar : PubMed/NCBI