Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2018

Open Access 01-12-2018 | Research

Safflower polysaccharide inhibits the development of tongue squamous cell carcinoma

Authors: Haiyan Zhou, Jing Yang, Chuhan Zhang, Yuwei Zhang, Rui Wang, Xiao Li, Shuainan Zhang

Published in: World Journal of Surgical Oncology | Issue 1/2018

Login to get access

Abstract

Background

Safflower polysaccharide (SPS) is one of the most important active components of safflower (Carthamus tinctorius L.), which has been confirmed to have the immune-regulatory function and antitumor effect. This study aimed to explore the effects of safflower polysaccharide (SPS) on tongue squamous cell carcinoma (TSCC).

Methods

HN-6 cells were treated with 5 μg/mL cisplatin and various concentrations of SPS (0, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28 mg/mL), and cell proliferation was measured. After treatment with 5 μg/mL cisplatin and 0.64 mg/mL SPS, the induction of apoptosis and the protein and mRNA expression of Bax, Bcl-2, COX-2, and cleaved caspase-3 in HN-6 cells were quantified. In addition, HN-6 cells were implanted into mice to establish an in vivo tumor xenograft model. Animals were randomly assigned to three groups: SPS treatment, cisplatin treatment, and the model group (no treatment). The body weight, tumor volume, and tumor weight were measured, and the expression of the above molecules was determined.

Results

SPS treatment (0.02–0.64 mg/mL) for 24–72 h inhibited HN-6 cell proliferation. In addition, 0.64 mg/mL SFP markedly induced apoptosis in HN-6 cells and arrested the cell cycle at the G0/G1 phase. Compared with the control group, the expression of Bcl-2 and COX-2 was markedly reduced by SPS treatment, whereas the expression of Bax and cleaved caspase-3 was increased. Moreover, SPS significantly inhibited the growth of the tumor xenograft, with similar changes in the expression of Bcl-2, COX-2, Bax, and cleaved caspase-3 in the tumor xenograft to the in vitro analysis.

Conclusions

Our results indicated that SPS may inhibit TSCC development through regulation of Bcl-2, COX-2, Bax, and cleaved caspase-3 expression.
Literature
1.
go back to reference Li H, Zhang Y, Chen SW, Li FJ, Zhuang SM, Wang LP, Zhang J, Song M. Prognostic significance of Flotillin1 expression in clinically N0 tongue squamous cell cancer. Int J Clin Exp Pathol. 2014;7:996–1003.PubMedPubMedCentral Li H, Zhang Y, Chen SW, Li FJ, Zhuang SM, Wang LP, Zhang J, Song M. Prognostic significance of Flotillin1 expression in clinically N0 tongue squamous cell cancer. Int J Clin Exp Pathol. 2014;7:996–1003.PubMedPubMedCentral
2.
go back to reference Cannon TL, Lai DW, Hirsch D, Delacure M, Downey A, Kerr AR, Bannan M, Andreopoulou E, Safra T, Muggia F. Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer? Oncologist. 2012;17:1541–6.CrossRefPubMedPubMedCentral Cannon TL, Lai DW, Hirsch D, Delacure M, Downey A, Kerr AR, Bannan M, Andreopoulou E, Safra T, Muggia F. Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer? Oncologist. 2012;17:1541–6.CrossRefPubMedPubMedCentral
3.
go back to reference Dibble EH, Alvarez ACL, Truong M-T, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med. 2012;53:709–15.CrossRefPubMed Dibble EH, Alvarez ACL, Truong M-T, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med. 2012;53:709–15.CrossRefPubMed
4.
go back to reference Trotta BM, Pease CS, Rasamny JJ, Raghavan P, Mukherjee S. Oral cavity and oropharyngeal squamous cell cancer: key imaging findings for staging and treatment planning. Radiographics. 2011;31:339–54.CrossRefPubMed Trotta BM, Pease CS, Rasamny JJ, Raghavan P, Mukherjee S. Oral cavity and oropharyngeal squamous cell cancer: key imaging findings for staging and treatment planning. Radiographics. 2011;31:339–54.CrossRefPubMed
5.
go back to reference Wakabayashi T, Hirokawa S, Yamauchi N, Kataoka T, Woo J-T, Nagai K. Immunomodulating activities of polysaccharide fractions from dried safflower petals. Cytotechnology. 1997;25:205–11.CrossRefPubMedPubMedCentral Wakabayashi T, Hirokawa S, Yamauchi N, Kataoka T, Woo J-T, Nagai K. Immunomodulating activities of polysaccharide fractions from dried safflower petals. Cytotechnology. 1997;25:205–11.CrossRefPubMedPubMedCentral
6.
go back to reference Ali Sahari M, Morovati N, Barzegar M, Asgari S. Physicochemical and antioxidant characteristics of safflower seed oil. Curr Nutr Food Sci. 2014;10:268–74.CrossRef Ali Sahari M, Morovati N, Barzegar M, Asgari S. Physicochemical and antioxidant characteristics of safflower seed oil. Curr Nutr Food Sci. 2014;10:268–74.CrossRef
7.
go back to reference Toma W, Guimarães LL, Brito AR, Santos AR, Cortez FS, Pusceddu FH, Cesar A, Júnior SL, Pacheco MT, Pereira CD. Safflower oil: an integrated assessment of phytochemistry, antiulcerogenic activity, and rodent and environmental toxicity. Revista Brasileira de Farmacognosia. 2014;24:538–44.CrossRef Toma W, Guimarães LL, Brito AR, Santos AR, Cortez FS, Pusceddu FH, Cesar A, Júnior SL, Pacheco MT, Pereira CD. Safflower oil: an integrated assessment of phytochemistry, antiulcerogenic activity, and rodent and environmental toxicity. Revista Brasileira de Farmacognosia. 2014;24:538–44.CrossRef
8.
go back to reference Sabah FS, Saleh AA. Evaluation of antibacterial activity of flavonoid and oil extracts from safflower (Carthamus tinctorius L). Evaluation. 2015;5:41–44. Sabah FS, Saleh AA. Evaluation of antibacterial activity of flavonoid and oil extracts from safflower (Carthamus tinctorius L). Evaluation. 2015;5:41–44.
9.
go back to reference Li L-J, Li Y-M, Qiao B-Y, Jiang S, Li X, Du H-M, Han P-C, Shi J. The value of safflower yellow injection for the treatment of acute cerebral infarction: a randomized controlled trial. Evid Based Complement Alternat Med. 2015;2015:478793.PubMedPubMedCentral Li L-J, Li Y-M, Qiao B-Y, Jiang S, Li X, Du H-M, Han P-C, Shi J. The value of safflower yellow injection for the treatment of acute cerebral infarction: a randomized controlled trial. Evid Based Complement Alternat Med. 2015;2015:478793.PubMedPubMedCentral
10.
go back to reference Fan S, Lin N, Shan G, Zuo P, Cui L. Safflower yellow for acute ischemic stroke: a systematic review of randomized controlled trials. Complement Ther Med. 2014;22:354–61.CrossRefPubMed Fan S, Lin N, Shan G, Zuo P, Cui L. Safflower yellow for acute ischemic stroke: a systematic review of randomized controlled trials. Complement Ther Med. 2014;22:354–61.CrossRefPubMed
11.
go back to reference Ando I, Tsukumo Y, Wakabayashi T, Akashi S, Miyake K, Kataoka T, Nagai K. Safflower polysaccharides activate the transcription factor NF-κB via Toll-like receptor 4 and induce cytokine production by macrophages. Int Immunopharmacol. 2002;2:1155–62.CrossRefPubMed Ando I, Tsukumo Y, Wakabayashi T, Akashi S, Miyake K, Kataoka T, Nagai K. Safflower polysaccharides activate the transcription factor NF-κB via Toll-like receptor 4 and induce cytokine production by macrophages. Int Immunopharmacol. 2002;2:1155–62.CrossRefPubMed
12.
go back to reference Shi X, Ruan D, Wang Y, Ma L, Li M. Anti-tumor activity of safflower polysaccharide (SPS) and effect on cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi=China journal of Chinese materia medica. 2010;35:215–8.PubMed Shi X, Ruan D, Wang Y, Ma L, Li M. Anti-tumor activity of safflower polysaccharide (SPS) and effect on cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi=China journal of Chinese materia medica. 2010;35:215–8.PubMed
13.
go back to reference Xi SY, Zhang Q, Wang C, Zhang JJ, Gao XM. Discussion of safflower inhibiting tumor in application and its mechanism of action. Ch inese Archives of Traditional Chinese Medicine. 2008;26:1916–7. Xi SY, Zhang Q, Wang C, Zhang JJ, Gao XM. Discussion of safflower inhibiting tumor in application and its mechanism of action. Ch inese Archives of Traditional Chinese Medicine. 2008;26:1916–7.
14.
go back to reference Luo Z, Zeng H, Ye Y, Liu L, Li S, Zhang J, Luo R. Safflower polysaccharide inhibits the proliferation and metastasis of MCF-7 breast cancer cell. Mol Med Rep. 2015;11:4611–6.CrossRefPubMed Luo Z, Zeng H, Ye Y, Liu L, Li S, Zhang J, Luo R. Safflower polysaccharide inhibits the proliferation and metastasis of MCF-7 breast cancer cell. Mol Med Rep. 2015;11:4611–6.CrossRefPubMed
15.
go back to reference SUN Y, YANG J, ZHANG Q-q, WANG X, XU F, LI M-z, WANG Y-x: Mechanism investigation of cell cycle arrest in hepatic cancer cell induced by safflower polysaccharide Chinese J Experimental Traditional Medical Formulae 2014; 13:046. SUN Y, YANG J, ZHANG Q-q, WANG X, XU F, LI M-z, WANG Y-x: Mechanism investigation of cell cycle arrest in hepatic cancer cell induced by safflower polysaccharide Chinese J Experimental Traditional Medical Formulae 2014; 13:046.
16.
go back to reference Li J-Y, Yu J, Du X-S, Zhang H-M, Wang B, Guo H, Bai J, Wang J-H, Liu A, Wang Y-L. Safflower polysaccharide induces NSCLC cell apoptosis by inhibition of the Akt pathway. Oncol Rep. 2016;36:147–54.CrossRefPubMed Li J-Y, Yu J, Du X-S, Zhang H-M, Wang B, Guo H, Bai J, Wang J-H, Liu A, Wang Y-L. Safflower polysaccharide induces NSCLC cell apoptosis by inhibition of the Akt pathway. Oncol Rep. 2016;36:147–54.CrossRefPubMed
17.
go back to reference Xinbo M, Zhenzuo Z, Rufei G, Xue-kui S, Lin S, An-wen Z, Hai-guang S, Shen Y, Ya-xian W. The pilot study on the inhibition of safflower polysaccharide to human gastric carcinoma cell line SGCY7901. Guangxi Medical J. 2012;34:1444Y6. Xinbo M, Zhenzuo Z, Rufei G, Xue-kui S, Lin S, An-wen Z, Hai-guang S, Shen Y, Ya-xian W. The pilot study on the inhibition of safflower polysaccharide to human gastric carcinoma cell line SGCY7901. Guangxi Medical J. 2012;34:1444Y6.
18.
go back to reference Wang T, Shi X, Sun Y, WANG Y-x: Experimental study on morphologic effect of safflower polysaccharide on the apoptosis of gastric carcinoma cell line SGC-7901. Information Traditional Chinese Medicine 2015; 32:19–21. Wang T, Shi X, Sun Y, WANG Y-x: Experimental study on morphologic effect of safflower polysaccharide on the apoptosis of gastric carcinoma cell line SGC-7901. Information Traditional Chinese Medicine 2015; 32:19–21.
19.
go back to reference Tao J, Li QW, Shi XK, Liang Y, Wang YX: Safflower polysaccharide inhibit PI3K/Akt signaling pathway induces apoptosis of human gastric cancer cells. Practical oncology Journal 2012; 26:119–124. Tao J, Li QW, Shi XK, Liang Y, Wang YX: Safflower polysaccharide inhibit PI3K/Akt signaling pathway induces apoptosis of human gastric cancer cells. Practical oncology Journal 2012; 26:119–124.
20.
go back to reference Liang A, Jianghong Z, Taijun Z, Xiaoqing L, Qiong Z, Jun C. Analysis of the inhibitory effect of safflower polysaccharide on HT29 colorectal cancer cell proliferation and its relevant mechanism. Biomed Res. 2017;28:2966–70. Liang A, Jianghong Z, Taijun Z, Xiaoqing L, Qiong Z, Jun C. Analysis of the inhibitory effect of safflower polysaccharide on HT29 colorectal cancer cell proliferation and its relevant mechanism. Biomed Res. 2017;28:2966–70.
21.
go back to reference Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99–104.CrossRefPubMed Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99–104.CrossRefPubMed
22.
go back to reference Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993;75:241–51.CrossRefPubMed Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993;75:241–51.CrossRefPubMed
23.
go back to reference Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281:E924–E30.CrossRefPubMed Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281:E924–E30.CrossRefPubMed
24.
go back to reference Tian X, Zeng G, Li X, Wu Z, Wang L. Cantharidin inhibits cell proliferation and promotes apoptosis in tongue squamous cell carcinoma through suppression of miR-214 and regulation of p53 and Bcl-2/Bax. Oncol Rep. 2015;33:3061–8.CrossRefPubMed Tian X, Zeng G, Li X, Wu Z, Wang L. Cantharidin inhibits cell proliferation and promotes apoptosis in tongue squamous cell carcinoma through suppression of miR-214 and regulation of p53 and Bcl-2/Bax. Oncol Rep. 2015;33:3061–8.CrossRefPubMed
25.
go back to reference Xin M, Li R, Xie M, Park D, Owonikoko TK, Sica GL, Corsino PE, Zhou J, Ding C, White MA. Small-molecule Bax agonists for cancer therapy. Nat Commun. 2014;5:4935.CrossRefPubMedPubMedCentral Xin M, Li R, Xie M, Park D, Owonikoko TK, Sica GL, Corsino PE, Zhou J, Ding C, White MA. Small-molecule Bax agonists for cancer therapy. Nat Commun. 2014;5:4935.CrossRefPubMedPubMedCentral
26.
go back to reference Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19:202–8.CrossRefPubMed Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19:202–8.CrossRefPubMed
27.
go back to reference LIU J, XU X f, YANG W j, Guo C y: Effect of safflower injection on proliferation, apoptosis, and expression of bcl-2/bax gene in hepatic stellate cell in vitro [J]. Chinese Traditional and Herbal Drugs 2009; 8:030. LIU J, XU X f, YANG W j, Guo C y: Effect of safflower injection on proliferation, apoptosis, and expression of bcl-2/bax gene in hepatic stellate cell in vitro [J]. Chinese Traditional and Herbal Drugs 2009; 8:030.
28.
go back to reference Lakhani SA, Masud A, Kuida K, Porter GA, Booth CJ, Mehal WZ, Inayat I, Flavell RA. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006;311:847–51.CrossRefPubMedPubMedCentral Lakhani SA, Masud A, Kuida K, Porter GA, Booth CJ, Mehal WZ, Inayat I, Flavell RA. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006;311:847–51.CrossRefPubMedPubMedCentral
29.
go back to reference Pan JA, Ullman E, Dou Z, Zong WX. Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes. Mol Cell Biol. 2011;31:3158–70.CrossRefPubMedPubMedCentral Pan JA, Ullman E, Dou Z, Zong WX. Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes. Mol Cell Biol. 2011;31:3158–70.CrossRefPubMedPubMedCentral
30.
go back to reference Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O'Sullivan B, He Z, Peng Y, Tan AC, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011;17:860–6.CrossRefPubMedPubMedCentral Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O'Sullivan B, He Z, Peng Y, Tan AC, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011;17:860–6.CrossRefPubMedPubMedCentral
31.
go back to reference Coutinho-Camillo CM, Lourenço SV, Nishimoto IN, Kowalski LP, Soares FA. Caspase expression in oral squamous cell carcinoma. Head & neck. 2011;33:1191–8.CrossRef Coutinho-Camillo CM, Lourenço SV, Nishimoto IN, Kowalski LP, Soares FA. Caspase expression in oral squamous cell carcinoma. Head & neck. 2011;33:1191–8.CrossRef
32.
go back to reference Khan Z, Khan N, P Tiwari R, K Sah N, Prasad G, S Bisen P. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets. 2011;12:1082–93.CrossRefPubMed Khan Z, Khan N, P Tiwari R, K Sah N, Prasad G, S Bisen P. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets. 2011;12:1082–93.CrossRefPubMed
33.
go back to reference Song X, Lin HP, Johnson AJ, Tseng PH, Yang YT, Kulp SK, Chen CS. Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst. 2002;94:585–91.CrossRefPubMed Song X, Lin HP, Johnson AJ, Tseng PH, Yang YT, Kulp SK, Chen CS. Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst. 2002;94:585–91.CrossRefPubMed
34.
go back to reference Cao J, Guo T, Dong Q, Zhang J, Li Y. miR-26b is downregulated in human tongue squamous cell carcinoma and regulates cell proliferation and metastasis through a COX-2-dependent mechanism. Oncol Rep. 2015;33:974–80.CrossRefPubMed Cao J, Guo T, Dong Q, Zhang J, Li Y. miR-26b is downregulated in human tongue squamous cell carcinoma and regulates cell proliferation and metastasis through a COX-2-dependent mechanism. Oncol Rep. 2015;33:974–80.CrossRefPubMed
35.
go back to reference Xu L, Stevens J, Hilton MB, Seaman S, Conrads TP, Veenstra TD, Logsdon D, Morris H, Swing DA, Patel NL. COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models. Sci Transl Med. 2014;6:242–ra84.CrossRef Xu L, Stevens J, Hilton MB, Seaman S, Conrads TP, Veenstra TD, Logsdon D, Morris H, Swing DA, Patel NL. COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models. Sci Transl Med. 2014;6:242–ra84.CrossRef
36.
go back to reference Wang CC, Choy CS, Liu YH, Cheah KP, Li JS, Wang JTJ, Yu WY, Lin CW, Cheng HW, Hu CM. Protective effect of dried safflower petal aqueous extract and its main constituent, carthamus yellow, against lipopolysaccharide-induced inflammation in RAW264. 7 macrophages. J Sci Food Agric. 2011;91:218–25.CrossRefPubMed Wang CC, Choy CS, Liu YH, Cheah KP, Li JS, Wang JTJ, Yu WY, Lin CW, Cheng HW, Hu CM. Protective effect of dried safflower petal aqueous extract and its main constituent, carthamus yellow, against lipopolysaccharide-induced inflammation in RAW264. 7 macrophages. J Sci Food Agric. 2011;91:218–25.CrossRefPubMed
Metadata
Title
Safflower polysaccharide inhibits the development of tongue squamous cell carcinoma
Authors
Haiyan Zhou
Jing Yang
Chuhan Zhang
Yuwei Zhang
Rui Wang
Xiao Li
Shuainan Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2018
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-018-1441-3

Other articles of this Issue 1/2018

World Journal of Surgical Oncology 1/2018 Go to the issue