Cancer Chemotherapy and Pharmacology

, Volume 56, Issue 1, pp 70–74 | Cite as

In vivo antitumor activity by 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone in a solid human carcinoma xenograft model

  • Chun-Lin Ye
  • Jian-Wen Liu
  • Dong-Zhi Wei
  • Yan-Hua Lu
  • Feng Qian
Original Article

Abstract

Previously we have shown that 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC), which is isolated from the buds of Cleistocalyx operculatus, significantly inhibits the growth of human liver cancer SMMC-7721 cells and is able to induce apoptosis of SMMC-7721 cells in vitro. Here we report the antitumor effects of DMC in vivo, using a solid human tumor xenograft mouse model using human liver cancer SMMC-7721 cells. The average tumor weights in the control group and in mice injected with 150 mg/kg DMC were 1.42±0.11 g and 0.59±0.12 g, respectively. Flow cytometric analysis of the tumor cell population demonstrated an aneuploid peak (representing 33.60±0.80% of the total in mice injected with 150 mg/kg DMC). To our knowledge, this is the first time that chalcone compounds have been applied to a human tumor xenograft model.

Keywords

Cleistocalyx operculatus Flavonoids Tumor Acute toxicity Xenograft 

References

  1. 1.
    Mori A, Nishino C, Enoki N, Tawata S (1988) Cytotoxicity of plant flavonoids against Hela cells. Phytochemistry 27:1017Google Scholar
  2. 2.
    Hirano T, Oka K, Akiba M (1989) Antiproliferative effects of synthetic and naturally occurring flavonoids on tumor cells of the human breast carcinoma cell ZR-75-1. Res Commun Chem Pathol Pharmacol 64:69Google Scholar
  3. 3.
    Lin YM, Chen FC, Lee KH (1989) Hinokiflavone, a cytotoxicity of the related biflavonoids. Planta Med 55:166Google Scholar
  4. 4.
    Cushman M, Nagarathnam D (1991) Cytotoxicities of some flavonoid analogues. J Nat Prod 54:1556Google Scholar
  5. 5.
    Woo AYH, Waye MMY, Kwan HS, Chan MCY, Chau CF, Cheng CHK (2002) Inhibition of ATPases by Cleistocalyx operculatus a possible mechanism for the cardiotonic action of the herb. Vasc Pharmacol 38:163Google Scholar
  6. 6.
    Ye CL, Lu YH, Wei DZ (2004) Flavonoids from Cleistocalyx operculatus. Phytochemistry 65:445Google Scholar
  7. 7.
    Yit CC, Das NP (1994) Cytotoxic effect of butein on human colon adenocarcinoma cell proliferation. Cancer Lett 82:65Google Scholar
  8. 8.
    Satomi Y (1993) Inhibitory effects of 3-methyl-3-hydroxychalcone on proliferation of human malignant tumor cells and on skin carcinogenesis. Int J Cancer 55:506Google Scholar
  9. 9.
    Wattenberg LW, Coccia JB, Galhaith AR (1994) Inhibition of carcinogen-induced pulmonary and mammary carcinogenesis by chalcone administered after carcinogen exposure. Cancer Lett 83:165Google Scholar
  10. 10.
    Edwards ML, Stemerick DM, Sunkara SP (1988) Chalcone derivatives useful in controlling growth of tumor tissue and their preparation. European Patent 288,794Google Scholar
  11. 11.
    Ye CL, Liu JW, Wei DZ, Lu YH, Qian F (2004) In vitro anti-tumor activity of 2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone against six established human cancer cell lines. Pharmacol Res 50:505Google Scholar
  12. 12.
    Lorke D (1983) A new approach to practical acute toxicity testing. Arch Toxicol 54:275Google Scholar
  13. 13.
    Liu JD, Chen SH, Lin CL, Tsai SH, Liang YC (2001) Inhibition of melanoma growth and metastasis by combination with (−)-epigallocatechin-3-gallate and dacarbazine in mice. J Cell Biochem 83:631Google Scholar
  14. 14.
    Fua LW, Zhang YM, Liang YJ, Yang XP, Pan QC (2002) The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinoma MCF-7/adr cells. Eur J Cancer 38:418CrossRefPubMedGoogle Scholar
  15. 15.
    Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271CrossRefPubMedGoogle Scholar
  16. 16.
    Anto RJ, Sukumara K, Kuttan G, Rao MNA, Subbaraju V, Kuttan R (1995) Anticancer and antioxidant of synthetic chalcones and related compounds. Cancer Lett 97:33Google Scholar
  17. 17.
    Parmar VS, Sharma NK, Husain M, Watterson AC, Kumar J, Samuelson LA, Cholli AL, Prasad AK, Kumar A, Malhotra S, Kumar N, Jha A, Singh A, Singh I, Himanshu, Vats A, Shakil NA, Trikha S, Mukherjee S, Sharma SK, Singh SK, Kumar A, Jha HN, Olsen CE, Stove CP, Brackef ME, Mareelf MM (2003) Synthesis, characterization and in vitro anti-invasive activity screening of polyphenolic and heterocyclic compounds. Bioorg Med Chem 11:913Google Scholar
  18. 18.
    Le Bail JC, Pouget C, Fagnere C, Basly JP, Chulia AJ, Habrioux G (2001) Chalcones are potent inhibitors of aromatase and 17β-hydroxysteroid dehydrogenase activities. Life Sci 68:751Google Scholar
  19. 19.
    Saydam G, Hakan Aydin H, Sahin F, Kucukoglu O, Ericiyas E, Terzioglu E, Buyukkececi F, Bedii Omay S (2003) Cytotoxic and inhibitory effects of 4′,4′-dihydroxy chalcone (RVC-588) on proliferation of human leukemic HL-60 cells. Leuk Res 27:57Google Scholar
  20. 20.
    Nam N, Kim Y, You Y, Hong D, Kim H, Ahn B (2003) Cytotoxic 2′,4′-dihydroxychalcones with unexpected antiangiogenic activity. Eur J Med Chem 38:179Google Scholar
  21. 21.
    Winograd B, Boven E, Lobbegoo MW, Pinedo HM (1987) Human tumor xenografts in the nude mouse and their value as test models in anti-cancer drug development. In Vivo 1:1Google Scholar
  22. 22.
    Havsteen BH (2002) The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96:67CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Chun-Lin Ye
    • 1
  • Jian-Wen Liu
    • 1
  • Dong-Zhi Wei
    • 1
  • Yan-Hua Lu
    • 1
  • Feng Qian
    • 1
  1. 1.State Key Laboratory of Bioreactor Engineering, Institute of Biochemistry East China University of Science and TechnologyShanghaiPeople’s Republic of China

Personalised recommendations