Planta Med 2009; 75(11): 1215-1220
DOI: 10.1055/s-0029-1185538
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

In vivo Inhibition of S180 Tumors by the Synergistic Effect of the Chinese Medicinal Herbs Coptis chinensis and Evodia rutaecarpa

Xiao-na Wang1 , Li-na Xu1 , Jin-yong Peng1 , 2 , Ke-xin Liu1 , Li-hua Zhang2 , Yu-kui Zhang2
  • 1College of Pharmacy, Dalian Medical University, Dalian, P. R. China
  • 2National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, P. R. China
Further Information

Publication History

received October 31, 2008 revised February 16, 2009

accepted February 26, 2009

Publication Date:
06 April 2009 (online)

Abstract

The aim of the present paper was to investigate the synergistic effect and mechanism of anticancer activity of Zuojinwan (ZJW) comprising Coptis chinensis Franch (HL) and Evodia rutaecarpa (Juss.) Benth (WZY) at a ratio of 6 : 1 (w/w). In vivo anticancer activity testing was carried out by inhibiting the growth of S180 tumor. Tumor growth inhibition, spleen index, lymphocyte proliferation, apoptosis, tumor necrosis factor-α (TNF-α) level, activities of serum tumor markers (TMs), increase in life span (ILS), histopathology and gene expression were tested. The results indicated that ZJW could significantly induce apoptosis of cancer cells. The inhibition ratio, ILS and TNF-α levels of mice treated with ZJW were 50.54 %, 64.91 % and 1.04 ng/mL, respectively, much higher than HL and WZY when singly used. Furthermore, the activities of acid phosphatase and alkaline phosphatase were significantly increased and the activities of creatine kinase, aldolase and lactate dehydrogenase were reduced in serum, and the expressions of Bax and wild-type p53 proteins were much higher for the mice treated by ZJW compared with HL and WZY single-treatment groups. A clear synergistic effect on the anticancer activity was observed with ZJW, and the mechanism of antitumor growth may be due to an effect on gene expression and activities of tumor markers in serum.

References

  • 1 Cai Q, Benson M A, Talbot T J, Devadas G, Swanson H J, Olson J L, Kirchner J P. Acute hepatitis due to fluoxetine therapy.  Mayo Clinic Proceedings. 1999;  74 692-694
  • 2 Stavrovskaya A A. Cellular mechanisms of multidrug resistance of tumor cells.  Biochem Russia. 2000;  65 95-106
  • 3 Kuo M T. Roles of multidrug resistance genes in breast cancer chemoresistance.  Adv Exp Med Biol. 2007;  608 23-30
  • 4 Shi L X, Ma R, Lu R, Xu Q, Zhu Z F, Wang L, Zhou C L, Li X L, Zhang H L, Yao Z. Reversal effect of tyroservatide (YSV) tripeptide on multi-drug resistance in resistant human hepatocellular carcinoma cell line BEL-7402/5-FU.  Cancer Lett. 2008;  269 101-110
  • 5 Tahiliani P, Kar A. The combined effects of Trigonella and Allium extracts in the regulation of hyperthyroidism in rats.  Phytomedicine. 2003;  10 665-668
  • 6 China Pharmacopoeia Committee .Pharmacopoeia of the People's Republic of China, the first division of 2005 edition. Beijing; China Chemical Industry Press 2005: 412-413
  • 7 Yang F Q, Zhang T Y, Zhang R, Ito Y. Application of analytical and preparative high-speed counter-current chromatography for separation of alkaloids from Coptis chinensis Franch.  J Chromatogr A. 1998;  829 137-141
  • 8 Kuo C L, Chi C W, Liu T Y. The anti-inflammatory potential of berberine in vitro and in vivo.  Cancer Lett. 2004;  203 127-137
  • 9 Wu C C, Chan Y C, Shuenn J S. Determination of the alkaloids in Evodiae Fructus by high-performance liquid chromatography.  J Chromatogr A. 1996;  727 317-323
  • 10 Wang L, Hu C P, Deng P Y, Shen S S, Zhu H Q, Ding J S, Tan G S, Li Y J. The protective effects of rutaecarpine on gastric mucosa injury in rats.  Planta Med. 2005;  71 416-419
  • 11 Ko H C, Wang Y H, Liou K T, Chen C M, Chen C H, Wang W Y, Chang S, Hou Y C, Chen K T, Chen C F, Shen Y C. Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells.  Eur J Pharmacol. 2007;  555 211-217
  • 12 Yu L L, Liao J F, Chen C F. Anti-diarrheal effect of water extract of Evodiae fructus in mice.  J Ethnopharmacol. 2000;  73 39-45
  • 13 Wang X N, Han X, Xu L N, Yin L H, Xu Y W, Qi Y, Peng J Y. Enhancement of apoptosis of human hepatocellular carcinoma SMMC-7721 cells through synergy of berberine and evodiamine.  Phytomedicine. 2008;  15 1062-1068
  • 14 Lv X, Wang J, Jiang W Q, Zhang H Y. Progress in the research of Coptis chinensis Franch.  Shangdong Industry Med. 2003;  22 33-35
  • 15 Zhou Y B, Xiong M, Han J, Zhang K. Progress in the research of alkaloids in Evodia rutaecarpa.  J Wengshan Teachers College. 2008;  21 102-107
  • 16 Xu S Y, Bian R L, Chen X. Experimental methodology of pharmacology. Beijing; People's Medical Publishment House 2002: 179
  • 17 China Pharmacopoeia Committee .Pharmacopoeia of the People's Republic of China, the first division of 2005 edition. Beijing; China Chemical Industry Press 2005: 412
  • 18 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
  • 19 Pedrycz A, Czerny K. Immunohistochemical study of proteins linked to apoptosis in rat fetal kidney cells following pre-pregnancy adriamycin administration in the mother.  Acta Histochem. 2008;  110 519-523
  • 20 Hoffmann S, Rockenstein A, Ramaswamy A, Celik I, Wunderlich A, Lingelbach S, Hofbauer L C, Zielke A. Retinoic acid inhibits angiogenesis and tumor growth of thyroid cancer cells.  Mol Cell Endocrinol. 2007;  264 74-81
  • 21 Das T, Mallick S K, Paul D, Bhutia S K, Bhattacharyya T K, Maiti T K. Microcontact printing of concanavalin A and its effect on mammalian cell morphology.  J Colloid Interface Sci. 2007;  314 71-79
  • 22 Xiong C, Chen X, Guo H L, Yang J. The use of AO/EB double staining for detection of apoptosis.  J Yunyang Med College. 1997;  2 68-72
  • 23 Zhang J H, Wan M X, Pan B R, Yu B. Cytotoxicity of HSVtk and hrTNF-α fusion genes with IRES in treatment of gastric cancer.  Cancer Lett. 2006;  235 191-201
  • 24 Hayes D F. Tumor marker development: towards validation of clinically useful markers.  Eur J Cancer Suppl. 2007;  5 77-81
  • 25 Thangaraju M, Sharma K, Liu D, Shen S H, Srikant C B. Interdependent regulation of intracellular acidification and SHP‐1 in apoptosis.  Cancer Res. 1999;  59 1647-1654
  • 26 Usui A, Fujita K, Imaizumi M, Abe T, Inoue K, Matumoto S, Kato K. Determination of creatine kinase isozymes in sera and tissues of patients with various lung carcinomas.  Clin Chim Acta. 1987;  164 47-53
  • 27 Fantin V R, St-Pierre J, Leder P. Attenuation of LDH‐A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance.  Cancer Cell. 2006;  9 425-434
  • 28 Kim E, Giese A, Deppert W. Wild-type p53 in cancer cells: when a guardian turns into a blackguard.  Biol Pharmacol. 2009;  77 11-20
  • 29 Smith N D, Rubenstein J N, Eggener S E, Kozlowski J M. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer.  J Urol. 2003;  169 1219-1228

Dr. Jinyong Peng

College of Pharmacy
Dalian Medical University

No. 9 West Part of Lvshun South Road

Dalian 116044

People's Republic of China

Phone: + 86 4 11 86 11 04 11

Fax: + 86 4 11 86 11 04 11

Email: jinyongpeng2005@163.com

Dr. Lihua Zhang

National Chromatographic Research and Analysis Center
Dalian Institute of Chemical Physics
The Chinese Academy of Sciences

No. 457 Zhongshan Road

Dalian 116 023

People's Republic of China

Phone: + 86 4 11 84 37 97 79

Fax: + 86 4 11 84 37 97 79

Email: lihuazhang@dicp.ac.cn

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