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Effects of Chitosan on Anti-tumor Activity in Mice

키토산이 암세포성장에 미치는 효과

  • 정양숙 (고신대학교 의과대학 미생물학교실) ;
  • 김광혁 (고신대학교 의과대학 미생물학교실) ;
  • 정영기 (동의대학교 자연과학대학 생명응용과학과) ;
  • 장명웅 (고신대학교 의과대학 미생물학교실)
  • Published : 2004.04.01

Abstract

Cytotoxic anticancer chemotherapeutic agents generally produce severe side effects, while reducing host resistance to cancer and infections, especially through the destruction of lymphoid and bone marrow cells. In this study, we have investigated the effect of chitosan on cytotoxic activity against cancer cells and life span in mice. The direct cytotoxicity of chitosan or chitosan-combinated chemotherapeutic agents for tumor cells was observed. In addition, the effect of life span extention was counted on sarcoma 180 mice injected with chitosan-combinated mitomycin C. The effect of growth inhibion for cancer cells, K562 and Yac-1 was shown in the cytotoxicity test of chitosan or chitosan-combinated chemotherapeutic agents. Also, the effect of life span extension was observed on sarcoma 180 mice injected with chitosan-combinated mitomycin C. Our results suggest that life span extension in sarcom 180 mice exposed with chitosan-combinated chemotherapeutic agents showed the probability of its usefulness for cancer therapy if more research results were accumulated.

본 연구에서는 키토산이 암세포에 미치는 효과를 보기 위하여 암세포에 대한 세포독성효과, 키토산을 기존 항암제와 함께 사용하였을 때의 암세포에 대한 세포독성효과 및 암마우스에 대한 생명연장 효과의 변화를 관찰하여 암 치료 가능성을 조사하고자 하였다. 암세포인 K562세포나 Yac-1세포에 키토산을 단독으로 작용시켰을 때 암세포성장억제효과를, 기존항암제(mitomycin C, cisplatin, 5-fluorouracil)와 복합으로 작용시켰을 때 암세포성장억제효과의 상승효과를 보이고 암 마우스에서 키토산을 기존항암제와 복합으로 투여한 결과 생명연장효과를 보였다. 따라서 이러한 결과들은 앞으로의 추가적인 연구결과들이 있게 되면 임상에서의 암 치료에 키토산의 이용가능성을 시사한다 하겠다.

Keywords

References

  1. Int. J. Pharm v.235 Design and evaluation of a mucoadhesive therapeutic agent delivery system for postoperative chemotherapy in superficial bladder cancer Eroglu,M.;S.Irmak;A.Acar;E.B.Denkbas https://doi.org/10.1016/S0378-5173(01)00979-6
  2. Jpn. J. Cancer Res. v.78 Enhanced anticancer efficacy by use of mitomycin C adsorbed on small activated carbon particles in mice Hagiwara,A.;T.Takahashi;T.Ueda;Y.Nakagawa
  3. Jpn. J. Cancer Res. v.92 Chitosan induces apoptosis via caspase-3 activation in bladder tumor cells Hasegawa,M.;K.Yagi,S.;Iwakawa,M.Hirai https://doi.org/10.1111/j.1349-7006.2001.tb01116.x
  4. Biomaterials v.22 The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro Howling,G.I.;P.W.Dettmar;P.A.Goddard;F.C.Hampson;M.Dornish;E.J.Wood https://doi.org/10.1016/S0142-9612(01)00042-4
  5. Vaccine v.9585 Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice Iqbal,M.;W.Lin;I.Jabbal-Gill;S.S.Davis;M.W.Steward;L.Illum
  6. J. Microencapsul v.14 Chitosan: properties, preparations and application to microparticulate systems Kas,H.S. https://doi.org/10.3109/02652049709006820
  7. J. Pharm. Pharmacol v.54 Efficacy of lactosaminated and intact N-succinyl-chitosan-mitomycin C conjugates against M5076 liver metastatic cancer Kato,Y.;H.Onishi;Y.Machida https://doi.org/10.1211/0022357021778646
  8. Int. J. Pharm v.226 Lactosaminated and intact N-succinyl-chitosans as drug carriers in liver metastasis Kato,Y.;H.Onishi;Y.Machida https://doi.org/10.1016/S0378-5173(01)00777-3
  9. Jpn. J. Cancer Res. v.90 Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice Kimura,Y.;H.Okuda https://doi.org/10.1111/j.1349-7006.1999.tb00813.x
  10. J. Pharmacol v.53 Antitumor activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumor-bearing mice Kimura,Y.;N.Sawai;H.Okuda https://doi.org/10.1211/0022357011777873
  11. Nutrition Res. v.18 Chitin-chitosan: properties, benefits, and risks Koide,S.S. https://doi.org/10.1016/S0271-5317(98)00091-8
  12. J. Vet. Med. Sci. v.58 Effect of chitosan implantation on activation of canine macrophages and polymorphonuclear cells after surgical stress Kosaka,T.;Y.Kaneko;Y.Nakada;M.Matsuura;S.Tanaka https://doi.org/10.1292/jvms.58.10_963
  13. Chem. Pharm. Bull. v.40 A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: antitumor effect of cis-diamminedichloroplatinum (Ⅱ) albumin microspheres, containing chitin and treated with chitosan on rabbits with VX2 hepatic tumors Kyotani,S.;Y.Nishioka;M.Okamura;T.Tanaka;M.Miyazaki;S.Ohnishi;Y.Yamamoto;K.Ito;T.Ogiso;S.Tanaka https://doi.org/10.1248/cpb.40.2814
  14. J. Conf. Rel. v.74 Tumor targeted delivery of encapsulated dextran-doxoru-bicin conjugate using chitosan nanoparticles as carrier Mitra,S.;U.Gaur;P.C.Ghosh;A.N.Maitra https://doi.org/10.1016/S0168-3659(01)00342-X
  15. Pharm. Res. v.15 Development of novel chitosan derivatives as micellar carriers of taxol Miwa,A.;A.Ishibe;M.Nakano;T.Yamahira;S.Itai;S.Jinno;H.Kawahara https://doi.org/10.1023/A:1011901921995
  16. Mol. Biother. v.2 Effect of chitin heparinoids on the activation of peritoneal macrophages and on the production of monokines in mice Nishimura,K.;S.Nishimura;N.Nishi;S.Tokura;I.Azuma
  17. Leuk. Res. v.25 Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer Pae,H.O.;W.G.Seo;N.Y.Kim;G.S.Oh;G.E.Kim;Y.H.Kim;H.J.Kwak;Y.G.Yun;C.D.Jun;H.T.Chung https://doi.org/10.1016/S0145-2126(00)00138-7
  18. Biomaterials v.15 Chitosan-mediated stimulation of macrophage function Peluso,G.;O.Petillo;M.Ranieri;M.Santin;L.Ambrosio;D.Calabro;B.Avallone;G.Balsamo https://doi.org/10.1016/0142-9612(94)90272-0
  19. Vaccine v.19 Immune stimulating activity of two new chitosan containing adjuvant formulations Seferian,P.G.;M.L.Martinez https://doi.org/10.1016/S0264-410X(00)00248-6
  20. Eur. J. Pharm. Biopharm. v.53 In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutroncapture therapy of cancer Shikata,F.;H.Tokumitsu;H.Ichikawa;Y.Fukumori https://doi.org/10.1016/S0939-6411(01)00198-9
  21. Biol. Pharm. Bull. v.16 Pharmacokinetic charateristics and antitumor activity of the N-succinyl-chitosan-mitomycin C conjugate and the carboxymethyl-chitin-mitomycin C conjugate Song,Y.;H.Onishi;T.Nagai https://doi.org/10.1248/bpb.16.48
  22. Carbohydr. Res. v.151 Antitumor effect of hexa-N-acetyl-chitohexaose Suzuki,K.;T.Mikami;Y.Okawa;A.Tokoro;S.Suzuki;M.Suzuki https://doi.org/10.1016/S0008-6215(00)90359-8
  23. Biomaterials v.18 Effect of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro Takashi,M.;O.Masahiro;M.Mitsunobu;U.Keisuke;T.Seiichi;O.Yoshiharu;M.Sabro;F.Toru https://doi.org/10.1016/S0142-9612(97)00017-3
  24. Adv. Drug Deliv. Rev. v.52 Topical formulation and wound healing applications of chitosan Ueno,H.;T.Mori;T.Fujinaga https://doi.org/10.1016/S0169-409X(01)00189-2
  25. J. Vet. Med. Sci. v.56 Chitin and chitosan induce migration of bovine polymorphonuclear cells Usami,Y.;Y.Okmoto;S.Minami;A.Matsuhashi;N.H.Kumazaws;S.Tanioka;Y.Shigemasa https://doi.org/10.1292/jvms.56.761
  26. Vaccine v.3600 Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice van der Lubben,I.M.;G.Kersten;M.M.Fretz;C.Beuvery;J.C.Verhoef;H.E.Junginger
  27. Vaccine v.20 Projuvant (Pluronic F127 /chitosan) enhances the immune response to intranasally administered tetanus toxoid Westerink,M.A.J.;S.L.Smithson;N.Srivastava;J.Blonder;C.Coeshott;G.J.Rosenthal https://doi.org/10.1016/S0264-410X(01)00423-6