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Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

Authors: Ze Tian, Jianyong Si, Qi Chang, Liang Zhou, Shilin Chen, Peigen Xiao, Erxi Wu

Published in: BMC Cancer | Issue 1/2007

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Abstract

Background

Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.

Methods

The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo.

Results

The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 μg/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner.

Conclusion

TGA may potentially find use as a new therapy for the treatment of hepatoma.
Appendix
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Literature
1.
go back to reference Marrero JA: Hepatocellular carcinoma. Curr Opin Gastroenterol. 2006, 22: 248-253. 10.1097/01.mog.0000218961.86182.8c.CrossRefPubMed Marrero JA: Hepatocellular carcinoma. Curr Opin Gastroenterol. 2006, 22: 248-253. 10.1097/01.mog.0000218961.86182.8c.CrossRefPubMed
2.
go back to reference Okita K: Clinical Aspects of Hepatocellular Carcinoma in Japan. Intern Med. 2006, 45: 229-233. 10.2169/internalmedicine.45.1531.CrossRefPubMed Okita K: Clinical Aspects of Hepatocellular Carcinoma in Japan. Intern Med. 2006, 45: 229-233. 10.2169/internalmedicine.45.1531.CrossRefPubMed
3.
go back to reference Bosch X, Ribes J, Borras J: Epidemiology of primary liver cancer. Semin Liver Dis. 1999, 19: 271-285.CrossRefPubMed Bosch X, Ribes J, Borras J: Epidemiology of primary liver cancer. Semin Liver Dis. 1999, 19: 271-285.CrossRefPubMed
4.
go back to reference Zhu AX: Hepatocellular carcinoma: are we making progress?. Cancer Invest. 2003, 21: 418-428. 10.1081/CNV-120018233.CrossRefPubMed Zhu AX: Hepatocellular carcinoma: are we making progress?. Cancer Invest. 2003, 21: 418-428. 10.1081/CNV-120018233.CrossRefPubMed
5.
go back to reference Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S, Tateishi R, Teratani T, Shiina S, Omata M: Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2006, 106 (9): 1990-1997. 10.1002/cncr.21832.CrossRefPubMed Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S, Tateishi R, Teratani T, Shiina S, Omata M: Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2006, 106 (9): 1990-1997. 10.1002/cncr.21832.CrossRefPubMed
6.
go back to reference Pharmacopoeia Commission of the People's Republic of China. The Pharmacopoeia of the People's Republic of China. 2000, Chemical Industry Publishing House: Beijing, 55- Pharmacopoeia Commission of the People's Republic of China. The Pharmacopoeia of the People's Republic of China. 2000, Chemical Industry Publishing House: Beijing, 55-
7.
go back to reference Li CJ, Chen DH, Xiao PG: [Chemical constituents of traditional Chinese drug "sheng-ma" (Cimicifuga dahurica)]. Yao Xue Xue Bao. 1993, 28 (10): 777-781. [Article in Chinese]PubMed Li CJ, Chen DH, Xiao PG: [Chemical constituents of traditional Chinese drug "sheng-ma" (Cimicifuga dahurica)]. Yao Xue Xue Bao. 1993, 28 (10): 777-781. [Article in Chinese]PubMed
8.
go back to reference Li CJ, Chen DH, Xiao PG: Chemical Constituents of Traditional Chinese Drug Sheng-ma (Cimicifuga Dahurica) III Structures of Cimiside C and Cimiside D. Acta Chimica Sinica. 1994, 52: 722-726. Li CJ, Chen DH, Xiao PG: Chemical Constituents of Traditional Chinese Drug Sheng-ma (Cimicifuga Dahurica) III Structures of Cimiside C and Cimiside D. Acta Chimica Sinica. 1994, 52: 722-726.
9.
go back to reference Liu Y, Chen DH, Si JY, Tu GZ, An DG: Two new cyclolanstanol xylosides from the aerial parts of Cimicifuga dahurica. J Nat Prod. 2002, 65: 1486-1488. 10.1021/np020130g.CrossRefPubMed Liu Y, Chen DH, Si JY, Tu GZ, An DG: Two new cyclolanstanol xylosides from the aerial parts of Cimicifuga dahurica. J Nat Prod. 2002, 65: 1486-1488. 10.1021/np020130g.CrossRefPubMed
10.
go back to reference Ye WC, Zhang JW, CheU CT, Ye T, Zhao SX: New Cycloartane Glycosides from Cimicifuga dahurica . Planta Med. 1999, 65: 770-772. 10.1055/s-2006-960865.CrossRefPubMed Ye WC, Zhang JW, CheU CT, Ye T, Zhao SX: New Cycloartane Glycosides from Cimicifuga dahurica . Planta Med. 1999, 65: 770-772. 10.1055/s-2006-960865.CrossRefPubMed
11.
go back to reference Lin X, Cai YF, Xiao PG: The effect of cimicifuga dahurica saponins on SCE frequency induced by MMC in peripheral lymphocytes of human. Aibian Jibian Tubian. 1994, 6: 30-3. Lin X, Cai YF, Xiao PG: The effect of cimicifuga dahurica saponins on SCE frequency induced by MMC in peripheral lymphocytes of human. Aibian Jibian Tubian. 1994, 6: 30-3.
12.
go back to reference Lin X, Cai YF, Xiao PG: Inhibition of SIV in vitro by cimicifuga dahurica and its action mechanism. Hua Xi Yao Xue Za Zhi. 1994, 9: 221-4. Lin X, Cai YF, Xiao PG: Inhibition of SIV in vitro by cimicifuga dahurica and its action mechanism. Hua Xi Yao Xue Za Zhi. 1994, 9: 221-4.
13.
go back to reference Tian Z, Yang MS, Huang F, Li KG, Si JY, Shi L, Xiao PG: Cytotoxicity of cyclartane triterpenoids from cimicifuga dahurica . Cancer lett. 2005, 226: 65-75. 10.1016/j.canlet.2004.11.019.CrossRefPubMed Tian Z, Yang MS, Huang F, Li KG, Si JY, Shi L, Xiao PG: Cytotoxicity of cyclartane triterpenoids from cimicifuga dahurica . Cancer lett. 2005, 226: 65-75. 10.1016/j.canlet.2004.11.019.CrossRefPubMed
14.
go back to reference Chang Q, Chen DH, Si JY, Shen LG: Determination of total triterpene glycosides content in Siraitia grosvenorii. Zhongguo Zhong Yao Za Zhi. 1995, 20: 554-5. Chang Q, Chen DH, Si JY, Shen LG: Determination of total triterpene glycosides content in Siraitia grosvenorii. Zhongguo Zhong Yao Za Zhi. 1995, 20: 554-5.
15.
go back to reference Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R: Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat. 2004, 84: 151-160. 10.1023/B:BREA.0000018413.98636.80.CrossRefPubMed Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R: Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat. 2004, 84: 151-160. 10.1023/B:BREA.0000018413.98636.80.CrossRefPubMed
16.
go back to reference Carmichael J, DeGraff WC, Gazdar AF: Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity. Cancer Res. 1987, 47: 936-942.PubMed Carmichael J, DeGraff WC, Gazdar AF: Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity. Cancer Res. 1987, 47: 936-942.PubMed
17.
go back to reference Chan HL, Liu HQ, Tzeng BC, You YS, Peng SM, Yang M, Che CM: Syntheses of ruthenium (II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity. Inorg Chem. 2002, 41: 3161-3171. 10.1021/ic0112802.CrossRefPubMed Chan HL, Liu HQ, Tzeng BC, You YS, Peng SM, Yang M, Che CM: Syntheses of ruthenium (II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity. Inorg Chem. 2002, 41: 3161-3171. 10.1021/ic0112802.CrossRefPubMed
18.
go back to reference Tian Z, Xu LJ, Chen SB, Zhou L, Yang MS, Chen SL, Xiao PG, Wu E: Cytotoxic activity of Schisandrolic and Isoschisandrolic acids involves induction of apoptosis. Chemotherapy. 2007, 53: 257-262. 10.1159/000102582.CrossRefPubMed Tian Z, Xu LJ, Chen SB, Zhou L, Yang MS, Chen SL, Xiao PG, Wu E: Cytotoxic activity of Schisandrolic and Isoschisandrolic acids involves induction of apoptosis. Chemotherapy. 2007, 53: 257-262. 10.1159/000102582.CrossRefPubMed
19.
go back to reference Tian Z, Lin G, Zheng RX, Yang MS, Xiao PG: Anti-hepatoma activity and mechanisms of components isolated from Aralia decaisneana. World J Gastroenterol. 2006, 12: 874-9.CrossRefPubMedPubMedCentral Tian Z, Lin G, Zheng RX, Yang MS, Xiao PG: Anti-hepatoma activity and mechanisms of components isolated from Aralia decaisneana. World J Gastroenterol. 2006, 12: 874-9.CrossRefPubMedPubMedCentral
20.
go back to reference Stolarska M, Mlynarski W, Zalewska-Szewczyk B, Bodalski J: Cytoprotective effect of amifostine in the treatment of childhood neoplastic diseases--a clinical study including the pharmacoeconomic analysis. Pharmacol Rep. 2006, 58 (1): 30-34.PubMed Stolarska M, Mlynarski W, Zalewska-Szewczyk B, Bodalski J: Cytoprotective effect of amifostine in the treatment of childhood neoplastic diseases--a clinical study including the pharmacoeconomic analysis. Pharmacol Rep. 2006, 58 (1): 30-34.PubMed
21.
go back to reference Srivastava JK, Gupta S: Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. Biochem Biophys Res Commun. 2006, 346: 447-453. 10.1016/j.bbrc.2006.05.147.CrossRefPubMed Srivastava JK, Gupta S: Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. Biochem Biophys Res Commun. 2006, 346: 447-453. 10.1016/j.bbrc.2006.05.147.CrossRefPubMed
22.
go back to reference Tian Z, Pan RL, Si JY, Xiao PG: Cytotoxicity of cycloartane triterpenoids from aerial part of Cimicifuga foetida . Fitoterapia. 2006, 77: 39-42. 10.1016/j.fitote.2005.08.001.CrossRefPubMed Tian Z, Pan RL, Si JY, Xiao PG: Cytotoxicity of cycloartane triterpenoids from aerial part of Cimicifuga foetida . Fitoterapia. 2006, 77: 39-42. 10.1016/j.fitote.2005.08.001.CrossRefPubMed
23.
go back to reference Yamahara J, Kobayashi M, Kimura H: Biologically active principles of crude drugs. The effect of Cimicifugae Rhizoma and constituents in preventive action on the carbon tetrachloride-induced liver disorder in mice. Shoyakugaku Zasshi. 1985, 39: 80-84. Yamahara J, Kobayashi M, Kimura H: Biologically active principles of crude drugs. The effect of Cimicifugae Rhizoma and constituents in preventive action on the carbon tetrachloride-induced liver disorder in mice. Shoyakugaku Zasshi. 1985, 39: 80-84.
24.
go back to reference Einbond LS, Shimizu M, Xiao D, Nuntanakorn P, Lim JT, Suzui M: Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells. Breast Cancer Res Treat. 2004, 83: 221-231. 10.1023/B:BREA.0000014043.56230.a3.CrossRefPubMed Einbond LS, Shimizu M, Xiao D, Nuntanakorn P, Lim JT, Suzui M: Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells. Breast Cancer Res Treat. 2004, 83: 221-231. 10.1023/B:BREA.0000014043.56230.a3.CrossRefPubMed
25.
go back to reference Einbond LS, Shimizu M, Nuntanakorn P, Seter C, Cheng R, Jiang B, Kronenberg F, Kennelly EJ, Weinstein IB: Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells. Planta Med. 2006, 72: 1200-1206. 10.1055/s-2006-947225.CrossRefPubMed Einbond LS, Shimizu M, Nuntanakorn P, Seter C, Cheng R, Jiang B, Kronenberg F, Kennelly EJ, Weinstein IB: Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells. Planta Med. 2006, 72: 1200-1206. 10.1055/s-2006-947225.CrossRefPubMed
26.
go back to reference Tian Z, Zhou L, Huang F, Chen SB, Xiao PG, Yang M, Wu E: Anticancer activity and mechanisms of 25-anhydrocimigenol-3-O-beta-D-xylopyranoside isolated from Souliea vaginata on hepatomas. Anti-cancer drugs. 2006, 17: 545-551. 10.1097/00001813-200606000-00008.CrossRefPubMed Tian Z, Zhou L, Huang F, Chen SB, Xiao PG, Yang M, Wu E: Anticancer activity and mechanisms of 25-anhydrocimigenol-3-O-beta-D-xylopyranoside isolated from Souliea vaginata on hepatomas. Anti-cancer drugs. 2006, 17: 545-551. 10.1097/00001813-200606000-00008.CrossRefPubMed
27.
go back to reference Cummings MC, Winterford CM, Walker NI: Apoptosis. Am J Surg Pathol. 1997, 21: 88-101. 10.1097/00000478-199701000-00010.CrossRefPubMed Cummings MC, Winterford CM, Walker NI: Apoptosis. Am J Surg Pathol. 1997, 21: 88-101. 10.1097/00000478-199701000-00010.CrossRefPubMed
28.
go back to reference Tong XH, Lin SG, Fujii M, Hou DX: Molecular mechanisms of echinocystic acid-induced apoptosis in HepG2 cells. Biochem Biophys Res Commun. 2004, 321: 539-546. 10.1016/j.bbrc.2004.07.004.CrossRefPubMed Tong XH, Lin SG, Fujii M, Hou DX: Molecular mechanisms of echinocystic acid-induced apoptosis in HepG2 cells. Biochem Biophys Res Commun. 2004, 321: 539-546. 10.1016/j.bbrc.2004.07.004.CrossRefPubMed
29.
go back to reference Zhong LT, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH, Bredesen DE: Bcl-2 inhibits death of central neural cell induced by multiple agents. Proc Natl Acad Sci. 1993, 90: 4533-4537. 10.1073/pnas.90.10.4533.CrossRefPubMedPubMedCentral Zhong LT, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH, Bredesen DE: Bcl-2 inhibits death of central neural cell induced by multiple agents. Proc Natl Acad Sci. 1993, 90: 4533-4537. 10.1073/pnas.90.10.4533.CrossRefPubMedPubMedCentral
30.
go back to reference Bruce-Keller AJ, Begley JG, Fu W, Butterfield DA, Bredesen DE, Hutchins JB, Hensley K, Mattson MP: Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J Neurochem. 1998, 70: 31-39.CrossRefPubMed Bruce-Keller AJ, Begley JG, Fu W, Butterfield DA, Bredesen DE, Hutchins JB, Hensley K, Mattson MP: Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J Neurochem. 1998, 70: 31-39.CrossRefPubMed
31.
go back to reference Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ: Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997, 139: 1281-1292. 10.1083/jcb.139.5.1281.CrossRefPubMedPubMedCentral Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ: Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997, 139: 1281-1292. 10.1083/jcb.139.5.1281.CrossRefPubMedPubMedCentral
32.
go back to reference Adams JM, Cory S: The Bcl-2 protein family arbiters of cell survival. Science. 1998, 281: 1322-1326. 10.1126/science.281.5381.1322.CrossRefPubMed Adams JM, Cory S: The Bcl-2 protein family arbiters of cell survival. Science. 1998, 281: 1322-1326. 10.1126/science.281.5381.1322.CrossRefPubMed
33.
go back to reference Zha H, Reed JC: Heterodimerization-independent functions of cell death regulatory proteins Bax and Bcl-2 in yeast and mammalian cells. J Biol Chem. 1997, 272: 31482-31488. 10.1074/jbc.272.50.31482.CrossRefPubMed Zha H, Reed JC: Heterodimerization-independent functions of cell death regulatory proteins Bax and Bcl-2 in yeast and mammalian cells. J Biol Chem. 1997, 272: 31482-31488. 10.1074/jbc.272.50.31482.CrossRefPubMed
Metadata
Title
Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma
Authors
Ze Tian
Jianyong Si
Qi Chang
Liang Zhou
Shilin Chen
Peigen Xiao
Erxi Wu
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-237

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