Skip to main content
Top
Published in: Tumor Biology 6/2015

01-06-2015 | Research Article

Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression

Authors: Fangfan Ye, Honghan Wang, Lusi Zhang, Yongyi Zou, Hailong Han, Jia Huang

Published in: Tumor Biology | Issue 6/2015

Login to get access

Abstract

Baicalein, a flavonoid compound, is one of the active constituents of the root of Scutellariae Radix. Its antitumor effects have attracted widespread attention worldwide. One of its major functions is to induce the apoptosis of tumor cells, but the antitumor mechanism is currently unclear. In the present study, we found that baicalein increased MG-63 cell mortality in a dose-dependent manner. Meanwhile, baicalein activated apoptosis through induced intracellular reactive oxygen species (ROS) generation, and that ROS scavenger N-acetyl-cysteine (NAC), glutathione (GSH), and superoxide dismutase (SOD) apparently inhibited intracellular ROS production, consequently attenuating the baicalein-induced apoptosis. Baicalein also induce the mitochondrial fragmentation which precedes the cell apoptosis. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 as well as Mul1 and Drp1. Furthermore, we show that the inhibition of BNIP3 expression can inhibit cell apoptosis by baicalein treatment. Taken together, our results bring the evidence of a mechanism that links apoptosis and ROS-induced BNIP3 expression in MG-63 cells with bacalein treatment and suggest that baicalein has a good potential as an anti-osteosarcoma drug.
Literature
1.
go back to reference Oertel S, Blattmann C, Rieken S, Jensen A, Combs SE, Huber PE, et al. Radiotherapy in the treatment of primary osteosarcoma—a single center experience. Tumori. 2010;96:582.PubMed Oertel S, Blattmann C, Rieken S, Jensen A, Combs SE, Huber PE, et al. Radiotherapy in the treatment of primary osteosarcoma—a single center experience. Tumori. 2010;96:582.PubMed
2.
go back to reference Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007;70:461–77.CrossRefPubMed Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007;70:461–77.CrossRefPubMed
3.
go back to reference Kim YO, Leem K, Park J, Lee P, Ahn D-K, Lee BC, et al. Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J Ethnopharmacol. 2001;77:183–8.CrossRefPubMed Kim YO, Leem K, Park J, Lee P, Ahn D-K, Lee BC, et al. Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J Ethnopharmacol. 2001;77:183–8.CrossRefPubMed
4.
go back to reference Chen Z-Y, Su Y-L, Lau C-W, Law W-I, Huang Y. Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Eur J Pharmacol. 1999;374:41–7.CrossRefPubMed Chen Z-Y, Su Y-L, Lau C-W, Law W-I, Huang Y. Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Eur J Pharmacol. 1999;374:41–7.CrossRefPubMed
5.
go back to reference Lin C-C, Shieh D-E. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. The American journal of Chinese medicine. 1996;24:31–6.CrossRefPubMed Lin C-C, Shieh D-E. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. The American journal of Chinese medicine. 1996;24:31–6.CrossRefPubMed
6.
go back to reference Waisundara VY, Siu SY, Hsu A, Huang D, Tan BK. Baicalin upregulates the genetic expression of antioxidant enzymes in type-2 diabetic Goto-Kakizaki rats. Life Sci. 2011;88:1016–25.CrossRefPubMed Waisundara VY, Siu SY, Hsu A, Huang D, Tan BK. Baicalin upregulates the genetic expression of antioxidant enzymes in type-2 diabetic Goto-Kakizaki rats. Life Sci. 2011;88:1016–25.CrossRefPubMed
7.
go back to reference Kim DH, Chung HY, Cho KH, Moon SK, Kim YS, Kim DH, et al. Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J Pharm Pharmacol. 2005;57:1581–90.CrossRefPubMed Kim DH, Chung HY, Cho KH, Moon SK, Kim YS, Kim DH, et al. Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J Pharm Pharmacol. 2005;57:1581–90.CrossRefPubMed
8.
go back to reference Chow J-M, Shen S-C, Wu C-Y, Chen Y-C. 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells. Apoptosis. 2006;11:1999–2011.CrossRefPubMed Chow J-M, Shen S-C, Wu C-Y, Chen Y-C. 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells. Apoptosis. 2006;11:1999–2011.CrossRefPubMed
9.
go back to reference Lee J-H, Li Y-C, Ip S-W, Hsu S-C, Chang N-W, Tang N-Y, et al. The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria-and caspase-3-dependent pathway. Anticancer Res. 2008;28:1701–11.PubMed Lee J-H, Li Y-C, Ip S-W, Hsu S-C, Chang N-W, Tang N-Y, et al. The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria-and caspase-3-dependent pathway. Anticancer Res. 2008;28:1701–11.PubMed
10.
go back to reference J-Y CHUANG, Y-Y TSAI, S-C CHEN, T-J HSIEH, J-G CHUNG. Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells. In Vivo. 2005;19:683–8. J-Y CHUANG, Y-Y TSAI, S-C CHEN, T-J HSIEH, J-G CHUNG. Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells. In Vivo. 2005;19:683–8.
11.
go back to reference Zhang H, Chen H, Luo H, An J, Sun L, Mei L, et al. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II. Hum Genet. 2012;131:491–503. doi:10.1007/s00439-011-1098-2.CrossRefPubMed Zhang H, Chen H, Luo H, An J, Sun L, Mei L, et al. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II. Hum Genet. 2012;131:491–503. doi:10.​1007/​s00439-011-1098-2.CrossRefPubMed
12.
go back to reference Wang J, Yu Y, Hashimoto F, Sakata Y, Fujii M, Hou D-X. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. International journal of molecular medicine. 2004;14:627.PubMed Wang J, Yu Y, Hashimoto F, Sakata Y, Fujii M, Hou D-X. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. International journal of molecular medicine. 2004;14:627.PubMed
13.
go back to reference Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochem. 2014;1–15. Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochem. 2014;1–15.
14.
go back to reference Ma W-D, Zou Y-P, Wang P, Yao X-H, Sun Y, Duan M-H, et al. Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway. Food Chem Toxicol. 2014;70:1–8.CrossRefPubMed Ma W-D, Zou Y-P, Wang P, Yao X-H, Sun Y, Duan M-H, et al. Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway. Food Chem Toxicol. 2014;70:1–8.CrossRefPubMed
15.
go back to reference Wu S, Zhou F, Zhang Z, Xing D. Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission–fusion proteins. FEBS J. 2011;278:941–54.CrossRefPubMed Wu S, Zhou F, Zhang Z, Xing D. Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission–fusion proteins. FEBS J. 2011;278:941–54.CrossRefPubMed
16.
go back to reference Ghavami S, Eshragi M, Ande SR, Chazin WJ, Klonisch T, Halayko AJ, et al. S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2009;20:314–31.CrossRefPubMedPubMedCentral Ghavami S, Eshragi M, Ande SR, Chazin WJ, Klonisch T, Halayko AJ, et al. S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2009;20:314–31.CrossRefPubMedPubMedCentral
17.
go back to reference Broadhead ML, Clark JC, Dass CR, Choong PF, Myers DE. Therapeutic targeting of osteoclast function and pathways. Expert Opin Ther Targets. 2011;15:169–81.CrossRefPubMed Broadhead ML, Clark JC, Dass CR, Choong PF, Myers DE. Therapeutic targeting of osteoclast function and pathways. Expert Opin Ther Targets. 2011;15:169–81.CrossRefPubMed
18.
go back to reference Takahashi H, Chen MC, Pham H, Angst E, King JC, Park J, et al. Baicalein, a component of Scutellaria baicalensis induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochimica et Biophysica Acta (BBA)-Molecular. Cell Res. 2011;1813:1465–74. Takahashi H, Chen MC, Pham H, Angst E, King JC, Park J, et al. Baicalein, a component of Scutellaria baicalensis induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochimica et Biophysica Acta (BBA)-Molecular. Cell Res. 2011;1813:1465–74.
19.
go back to reference Kuo H-M, Tsai H-C, Lin Y-L, Yang J-S, Huang A-C, Yang M-D, et al. Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells. Int J Oncol. 2009;35:717–24.PubMed Kuo H-M, Tsai H-C, Lin Y-L, Yang J-S, Huang A-C, Yang M-D, et al. Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells. Int J Oncol. 2009;35:717–24.PubMed
20.
go back to reference Zhang Y, Song L, Cai L, Wei R, Hu H, Jin W (2012) Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food Chem Toxicol. Zhang Y, Song L, Cai L, Wei R, Hu H, Jin W (2012) Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food Chem Toxicol.
21.
go back to reference Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35:57–68.CrossRefPubMed Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35:57–68.CrossRefPubMed
22.
go back to reference Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.CrossRefPubMed Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.CrossRefPubMed
23.
go back to reference Han Y, Chen JZ (2012) Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. BioMed Res Int 2013 Han Y, Chen JZ (2012) Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. BioMed Res Int 2013
24.
go back to reference Reed J. Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death & Differentiation. 2006;13:1378–86.CrossRef Reed J. Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death & Differentiation. 2006;13:1378–86.CrossRef
26.
go back to reference Jisun L, Samantha G, Jianhua Z. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441:523–40.CrossRef Jisun L, Samantha G, Jianhua Z. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441:523–40.CrossRef
Metadata
Title
Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression
Authors
Fangfan Ye
Honghan Wang
Lusi Zhang
Yongyi Zou
Hailong Han
Jia Huang
Publication date
01-06-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3122-y

Other articles of this Issue 6/2015

Tumor Biology 6/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine