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AN EXPERIMENTAL STUDY ON MISTLETOE EXTRACT-INDUCED APOPTOSIS IN ORAL SQUAMOUS CELL CARCINOMA  

Heo, Gyun-Haeng (Department of Oral & Maxillofacial Surgery, College of Dentistry, Dankook University)
Lee, Jae-Hoon (Department of Oral & Maxillofacial Surgery, College of Dentistry, Dankook University)
Kim, Chul-Hwan (Department of Oral & Maxillofacial Surgery, College of Dentistry, Dankook University)
Publication Information
Journal of the Korean Association of Oral and Maxillofacial Surgeons / v.31, no.1, 2005 , pp. 13-23 More about this Journal
Abstract
This study was performed to investigate mistletoe extract-induced apoptosis in oral squamous cell carcinoma. In vivo study, HN22 cells were xenografted in nude mice. After tumor was experimentally induced, mistletoe extract was directly injected on the tumor mass. The specimens were evaluated using light and transmission electron microscopes. In vitro study, HN22 cells were cultured and exposed to mistletoe extract. The cells were evaluated using transmissin electron microscope. To evaluate apoptotic cells, flow cytometric analysis was done. The results were obtained as follows: 1. Light microscopic view of tumor mass showed necrosis at 2-4 weeks. 2. Transmission electron micrographs of tumor mass showed apoptosis and necrosis. 3. In TEM view of cell lines, necrosis and apoptosis were shown with mistletoe extract at $300{\mu}g/ml$, apoptosis was shown with mistletoe extract at $100{\mu}g/ml$. 4. In flow cytometric analysis, early and late apoptosis was shown when using caspase-3Ab and annexin-V, but no significant change was noted when using mebstain and Apo2.7 Ab. In this study, mistletoe extract induced necrosis and apoptosis in the tumor mass was induced by HN22 cells, early and late apoptosis in vitro study. Mistletoe extract was likely to induce cell death in oral squamous cell carcinoma through apoptosis.
Keywords
Mistletoe Extract; Apoptosis; Oral Squamous Cell Carcinoma; HN22 cells; Flow cytometric analysis;
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1 Mansky PJ: Mistletoe and Cancer: controversies and perspectives. Seminar in Oncology Dec 2002;29(6):589-594
2 Franz H: Mistletoe lectins and their A and B chains. Oncology 1986;5 43:23-24   DOI   PUBMED   ScienceOn
3 Yokoda J: Tumor progression and metastasis. Carcinogenesis 2000;21:497-503   DOI   PUBMED   ScienceOn
4 Schewartz LM, Osborn BA: Programmed cell death, apoptosis and killer genes. Immunol Today 1993;14:582-590   DOI   ScienceOn
5 Antonsson B, Martinou JC: The Bcl-2 protein family. Exp Cell Res 2000;256:50-57   DOI   ScienceOn
6 Kim YS, Jin SH, Lee YH, et al.: Ginsenoside Rh2 induces apoptosis independently of Bcl-2, Bcl-XL or Bax in C6Bu-1 cells. Arc Pharm Res 1999;22:448-453   DOI   ScienceOn
7 Kelekar A, Thompson CB: Bcl-2 family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 1998;8:324-330   DOI   ScienceOn
8 Boise LH, Gonzalez-Garcia M, Postema CE, et al.: Bcl-xL, a bcl-2- related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993;74:597-608   DOI   ScienceOn
9 Ghayur T, Hugunin M, Talanian RV, et al.: Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis. J Exp Med 1996;184:2399-2404   DOI
10 Schulze-Osthoff K, Ferrari D, Los M, et al.: Apoptosis signaling by death receptors. Eur J Biochem 1998;254:439-459   DOI   ScienceOn
11 Majno G, Joris I: Apoptosis, oncosis, and necrosis, an overview of cell death. Am J Pathol 1995;146:3-15
12 Koester SK, Roth P, Mikulka WR, et al.: Monitoring early cellular responses in apoptosis is aided by the mitochondrial membrane protein specific monoclonal antibody Apo 2.7. Cytometry 1997;29:306- 312   DOI   ScienceOn
13 Martin SJ: Protein or RNA synthesis inhibiton induces apoptosis of mature human CD4+ T cell blasts. Immunol Lett 1993;35:125-134   DOI   PUBMED   ScienceOn
14 Park JH, Hyun CK, Shin HK: Cytotoxic effects of the components in heat-treated mistletoe (Viscum album). Cancer Lett 1999;139:207- 213   DOI   ScienceOn
15 Lowe SW, Lin AW: Apoptosis in cancer. Carcinogenesis 2000; 21:485-495   DOI   ScienceOn
16 Bussing A: Mistletoe: A story with an open end. Anticancer Drugs 1997;8(suppl.1):1-2
17 Peumans WJ, Verhaert P, Pf?ller U, et al.: Isolation and partial characterization of a small chintin-binding lection from mistletoe (Viscum-album). FEBS Lett 1996;396:261-265   DOI   PUBMED   ScienceOn
18 Forkman J, Klagsbrun M: Angiogenic factors. Science 1987;235:442- 447   DOI   PUBMED
19 Kimura C, Kondo OL, Amatsu M, et al.: Mechanism of UV-induced apoptosis in Human leukemia cells: roles of Ca2+/Mg2+ endonuclease, caspase-3, and stress-activated protein kinase. Exp Cell Res 1998;239:411-422   DOI   ScienceOn
20 Yonish-Rouach E, Resnizky D, Lotem J, et al.: Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin- 6. Nature 1991;352:345-347   DOI   ScienceOn
21 Stein GM, Berg PA: Mistletoe extract-Induced effects on Immunocompetent cells : In vitro study. Anticancer Drugs(Suppl 1): 1997;s39-42
22 Fillis RE, Yuan J, Horvitz HR: Mechanism and functions of cell death. Ann Rev Cell Biol 1991;7:663-698   DOI   ScienceOn
23 Krammer PH, Behnnann I, Daniel P, et al.: Regulation of apoptosis in the immune system. Curr Biol 1994;6:279-289   DOI   ScienceOn
24 Kroemer G, Zamzami N, Susin SA: Mitochondrial control of apoptosis. Immunol Today 1997;18:44-51   DOI   ScienceOn
25 Hodes R: Molecular targeting of cancer : Telomeres as targets. Proc Natl Acad Sci USA 2001;98:7649-7651
26 Kano A, Watanabe Y, Takeda N, et al.: Analysis of IFN-gammainduced cell cycle arrest and cell death in hepatocytes. J Biochem 1997;121:677-683   DOI   ScienceOn
27 Bussing A, Wagner M, Wagner B, et al.: Induction of mitochondrial Apo 2.7 molecules and generation of reactive oxygen-intermediates cultured lymphocytes by the toxic protein from Viscum album L. Cancer Lett 1999;139:79-88   DOI   ScienceOn
28 Schaller G, Urech K: Cytotoxicity and different viscotoxins and extracts from the europeans subspecies of Viscum album L. phytotheraphy Research 1996;10:473-477   DOI   ScienceOn
29 Kerr JFR, Winterford CM, Harmon BV: Apoptosis-its significance in cancer and cancer therapy. Cancer 1994;73:2013-2026   DOI   PUBMED   ScienceOn
30 Yoon TJ, Yoo YC, Choi OB, et al.: Inhibitory effect of Korean mistletoe(Viscum album coloratum) extract on tumor angiogenesis and metastasis of haematogenous and non-haematogenous tumor cells in mice. Cancer Lett 1995;97:83-91   DOI   ScienceOn
31 Lyu SY, Park WB, Choi KH, et al.: involvement of caspase-3 in apoptosis induced by Viscum album var. coloratum agglutinin in HL- 60 cells. Biosci Biotechnol Biochem 2001;65(3):534-541   DOI   ScienceOn
32 Liu JP: Studies on the molecular mechanisms in the regulation of telomerase activity. FASEB J 1999;13:2091-2104
33 Kovac S, Hajto T, Hostanska K: Improvement of DNA repair in lymphocytes of breast cancer patient treated with viscum album extract(Iscador). Eur J Cancer 1991;27:1672-1676   DOI
34 Kutan SAR, Kuttan G: Effect of Viscum album in the inhibition of lung metasis in mice induced by B 6F10 melanoma cells. J Exp Clin Cancer Res 1999;6:159-162
35 Jassen O, Scheffler A, Kabelitz D: In vitro effect of mistletoe extracts and mistletoe lectins. Drug Res 1993;43(11):1221-1227
36 Burger AM, Mengs U, Schuler JB, et al.: Antiproliferative activity of an aqueous mistletoe extract in human tumor cell line and xenografts in vitro. Drug Res 2001;51:748-757
37 Martin SJ, Green DR: Protease activation during apoptosis : death by a thousand cuts. Cell 1995;82:349-352   DOI   ScienceOn
38 Frauz H, Ziska P, kindt A: Isolation and properties of three lectin from misteletoe(Viscum album L.). J Biochem 1981;195:481-484
39 Overbeeke R, Steffens-Nakken H, Vermes I, et al.: Early feature of apoptosis detected by four different cytometric assay. Apoptosis 1998;3:11.5-121   DOI   ScienceOn
40 Kim WH, Kang KH, Kim MY, et al.: Induction of p53-independent p21 during ceramide-induced G1 arrest in human hepatocarcinoma cells. Biochem Cell Biol 2000;78:127-135   DOI   ScienceOn
41 Khwaja A, Tatton L: Caspase-mediated proteolysis and activation of protein kinase Cdelta plays a central role in neutrophil apoptosis. Blood 1999;94:291-301
42 Jiang H, Lin J, Su Z, Collart FR, et al.: Induction of Differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1 expression in the abscence of p53. Oncogene 1994;9:3397-3406
43 Folkman J: Tumour angiogenesis. Adv Cancer Res 1985;43:175-203   DOI   PUBMED   ScienceOn
44 Tereda N, Lucas JJ, Gelfand EW: Differential regulation of tumor suppressor molecules, retinoblastoma susceptibility gene product (Rb) and p53, during cell cycle progression of normal human T cells. J Immunol 1991;147:698-704
45 Hofmann B, Reed JC: Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994;9:1799- 1805
46 Emoto Y, Manome Y, Meinhardt G, et al.: Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J 1995;14:6148-6156
47 Alnemri ES, Livingston DJ, Nicholson DW, et al.: Human ICE/CED- 3 protease nomenclature(letter). Cell 1996;87:171   DOI   ScienceOn
48 Lizard GL, Fournel S, Genestier L, et al.: Kinetics of plasma membrane and mitochondrial alterations in cells undergoing apoptosis. Cytometry 1995;21:275-283   DOI   ScienceOn
49 Zhang C, Ao Z, Seth A, et al.: Mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells. J Immunol 1996;157:3980-3987
50 Kuirbitz SJ, Plunkett BS, Walsh WV, et al.: Wild type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 1992;89:7491-7495
51 El-Deiry WS, Harper JW, OConner PM, et al.: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994;54:1169-1174
52 Bocci V: Mistletoe(Viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. J Biol Reg Homeos Agent 1993;7:1-6
53 Wallance BRR, lowe SW: Clinical implications of mutations. Cell Mol Life Sci 1999;55:64-75   DOI   ScienceOn
54 Stein GM, Schaller G, Pfuller U: Thionins from Viscum album L : Influence of the viscotoxins on the activation of granulocytes. Anticancer Res 1999;19:1037-1042