Generation of reactive oxygen species mediates butein-induced apoptosis in neuroblastoma cells

Chen,Ya-Hui; Yeh,Chi-Wei; Lo,Hui-Chen; Su,Shih-Li; Hseu,You-Cheng; Hsu,Li-Sung

doi:10.3892/or.2012.1632

Generation of reactive oxygen species mediates butein-induced apoptosis in neuroblastoma cells

Authors:
- Ya-Hui Chen
- Chi-Wei Yeh
- Hui-Chen Lo
- Shih-Li Su
- You-Cheng Hseu
- Li-Sung Hsu
View Affiliations

Affiliations: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C., Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 402, Taiwan, R.O.C.
Published online on: January 12, 2012 https://doi.org/10.3892/or.2012.1632
Pages: 1233-1237

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Flavonoids exhibit chemopreventive and chemotherapeutic effects. Butein, a bioactive flavonoid isolated from numerous native plants, has been shown to induce apoptosis in human cancer cells. In the current study, the molecular mechanisms of butein action on cell proliferation and apoptosis of neuroblastoma cells were evaluated. Treatment with butein decreased the viability of Neuro-2A neuroblastoma cells in a dose- and time-dependent manner. The dose-dependent nature of butein-induced apoptosis was characterized by an increase in the sub-G1 phase population. Treatment with butein significantly increased intracellular reactive oxygen species (ROS)levels and reduced the Bcl-2/Bax ratio, triggering the cleavage of pro-caspase 3 and poly-(ADP-ribose) polymerase (PARP). Pre-treatment with the antioxidant agent, N-acetyl cysteine (NAC), blocks butein-induced ROS generation and cell death. NAC also recovers butein-induced apoptosis-related protein alteration. In conclusion, butein-triggered neuroblastoma cells undergo apoptosis via generation of ROS, alteration of the Bcl‑2/Bax ratio, and cleavage of pro-caspase 3 and PARP. Our results suggest that butein may serve as a potential therapeutic agent for the treatment of neuroblastoma.

View Figures

View References

1	Michalska M, Gluba A, Mikhailidis DP, Nowak P, Bielecka-Dabrowa A, Rysz J and Banach M: The role of polyphenols in cardiovascular disease. Med Sci Monit. 16:RA110–RA119. 2010.PubMed/NCBI
2	Enomoto T, Nagasako-Akazome Y, Kanda T, Ikeda M and Dake Y: Clinical effects of apple polyphenols on persistent allergic rhinitis: a randomized double-blind placebo-controlled parallel arm study. J Investig Allergol Clin Immunol. 16:283–289. 2006.PubMed/NCBI
3	Singh M, Arseneault M, Sanderson T, Murthy V and Ramassamy C: Challenges for research on polyphenols from foods in Alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. J Agric Food Chem. 56:4855–4873. 2008.PubMed/NCBI
4	Guo W, Kong E and Meydani M: Dietary polyphenols, inflammation, and cancer. Nutr Cancer. 61:807–810. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lee JC, Lee KY, Kim J, Na CS, Jung NC, Chung GH and Jang YS: Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells. Food Chem Toxicol. 42:1383–1388. 2004.
6	Jung CH, Jun CY, Lee S, Park CH, Cho K and Ko SG: Rhus verniciflua stokes extract: radical scavenging activities and protective effects on H₂O₂-induced cytotoxicity in macrophage RAW 264.7 cell lines. Biol Pharm Bull. 29:1603–1607. 2006. View Article : Google Scholar
7	Jung CH, Kim JH, Hong MH, Seog HM, Oh SH, Lee PJ, Kim GJ, Kim HM, Um JY and Ko SG: Phenolic-rich fraction from Rhus verniciflua Stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW 264.7 macrophages. J Ethnopharmacol. 110:490–497. 2007.
8	Yit CC and Das NP: Cytotoxic effect of butein on human colon adenocarcinoma cell proliferation. Cancer Lett. 82:65–72. 1994. View Article : Google Scholar : PubMed/NCBI
9	Jang HS, Kook SH, Son YO, Kim JG, Jeon YM, Jang YS, Choi KC, Kim J, Han SK, Lee KY, Park BK, Cho NP and Lee JC: Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochim Biophys Acta. 1726:309–316. 2005.PubMed/NCBI
10	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
11	Kim JH, Jung CH, Jang BH, Go HY, Park JH, Choi YK, Hong SI, Shin YC and Ko SG: Selective cytotoxic effects on human cancer cell lines of phenolic-rich ethyl-acetate fraction from Rhus verniciflua Stokes. Am J Chin Med. 37:609–620. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kim NY, Pae HO, Oh GS, Kang TH, Kim YC, Rhew HY and Chung HT: Butein, a plant polyphenol, induces apoptosis concomitant with increased caspase-3 activity, decreased Bcl-2 expression and increased Bax expression in HL-60 cells. Pharmacol Toxicol. 88:261–266. 2001. View Article : Google Scholar : PubMed/NCBI
13	Kim N: Butein sensitizes human leukemia cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Arch Pharm Res. 31:1179–1186. 2008. View Article : Google Scholar
14	Moon DO, Kim MO, Choi YH and Kim GY: Butein sensitizes human hepatoma cells to TRAIL-induced apoptosis via extracellular signal-regulated kinase/Sp1-dependent DR5 upregulation and NF-kappaB inactivation. Mol Cancer Ther. 9:1583–1595. 2010. View Article : Google Scholar
15	Chua AW, Hay HS, Rajendran P, Shanmugam MK, Li F, Bist P, Koay ES, Lim LH, Kumar AP and Sethi G: Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-kappaB activation in breast and pancreatic tumor cells. Biochem Pharmacol. 80:1553–1562. 2010. View Article : Google Scholar : PubMed/NCBI
16	Mueller S and Matthay KK: Neuroblastoma: biology and staging. Curr Oncol Rep. 11:431–438. 2009. View Article : Google Scholar
17	Llambi F and Green DR: Apoptosis and oncogenesis: give and take in the BCL-2 family. Curr Opin Genet Dev. 21:12–20. 2011. View Article : Google Scholar : PubMed/NCBI
18	Ola MS, Nawaz M and Ahsan H: Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 351:41–58. 2011. View Article : Google Scholar : PubMed/NCBI
19	Chang IC, Huang YJ, Chiang TI, Yeh CW and Hsu LS: Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells. Biol Pharm Bull. 33:816–824. 2010. View Article : Google Scholar
20	Juan ME, Wenzel U, Daniel H and Planas JM: Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem. 56:4813–4818. 2008. View Article : Google Scholar
21	Kelloff GJ, Boone CW, Crowell JA, Steele VE, Lubet R and Sigman CC: Chemopreventive drug development: perspectives and progress. Cancer Epidemiol Biomarkers Prev. 3:85–98. 1994.PubMed/NCBI
22	Khan N, Afaq F and Mukhtar H: Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal. 10:475–510. 2008. View Article : Google Scholar : PubMed/NCBI
23	Grassi D, Desideri G, Croce G, Tiberti S, Aggio A and Ferri C: Flavonoids, vascular function and cardiovascular protection. Curr Pharm Des. 15:1072–1084. 2009. View Article : Google Scholar : PubMed/NCBI
24	Cory S and Adams JM: The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI
25	Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M and Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 39:44–84. 2007. View Article : Google Scholar : PubMed/NCBI
26	Moon DO, Kim MO, Choi YH, Hyun JW, Chang WY and Kim GY: Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation. Cancer Lett. 288:204–213. 2010. View Article : Google Scholar : PubMed/NCBI