Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1996 Nov;87(11):1171–1178. doi: 10.1111/j.1349-7006.1996.tb03128.x

Lentinan Enhances Sensitivity of Mouse Colon 26 Tumor to cis‐Diamminedichloroplatinum(II) and Decreases Glutathione Transferase Expression

Tetsuo Murata 1, Ichiro Hatayama 1, Ikuko Kakizaki 1, Kimihiko Satoh 1, Kiyomi Sato 1, Shigeki Tsuchida 1,✉
PMCID: PMC5921014  PMID: 9045947

Abstract

We investigated the influence of a combination of lentinan, a biological response modifier, and cis‐diamminedichloroplatinum(II) (CDDP) on the growth and glutathione S‐transferase (GST) content of colon 26 tumor to examine whether lentinan represses GST expression and enhances the therapeutic effects of CDDP. Female CDF1 mice inoculated subcutaneously with transplantable colon 26 adenocarcinoma cells (1X106/mouse) received intraperitoneal administrations of lentinan, CDDP, or the two drugs in combination, on days 10, 14, 17 and 21 after the inoculation. On day 24, tumor weights (estimated from their length and width) were significantly lower in the CDDP+lentinan group (2.7±1.3g) than in the CDDP alone group (4.3±0.7g, p<0.05), both values being less than in the nontreated control group (7.2±1.5g). The major GST form of colon 26 tumor was identified as GST‐II, the Pi class form, and a minor form as GST‐III belonging to the Mu class. Both GST‐II and GST‐III values on day 24 were significantly decreased in the lentinan alone (0.90±0.29 and 0.26±0.11 μg/mg protein, respectively) and lentinan+CDDP groups (0.98±0.22 and 0.29±0.07 μg/mg protein), as compared with the control levels (1.39±0.20 and 0.52±0.11 μg/mg protein). However, these values were not different between the CDDP alone and lentinan+CDDP groups. Neither tissue interleukin (IL)‐6, glutathione nor platinum values were different between the two groups. IL‐6 values were elevated in about half of the samples treated with lentinan or CDDP and exhibited a modest inverse correlation with GST‐II levels (r= ‐ 0.46). A GST inhibitor, ethacrynic acid, enhanced the sensitivity of cultured colon 26 cells to CDDP, suggesting the possible involvement of GST in modulating the cytotoxicity of CDDP to this cell line. These results indicated that lentinan administration decreases tissue GST‐II and GST‐III contents and enhances the sensitivity of colon 26 tumor to CDDP.

Keywords: Glutathione transferase, Colon tumor, Drug resistance, cis—Diamminedichloroplatinum(II), Biological response modifier

Full Text

The Full Text of this article is available as a PDF (481.3 KB).

REFERENCES

  • 1. ) Loehrer , P. J. and Einhorn , L. H.Diagnosis and treatment ‐ drugs five years later: cisplatin . Ann. Intern. Med. , 100 , 704 – 713 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Teicher , B. A. , Holden , S. A , Kelley , M. J. , Shea , T. C. , Cucchi , C. A. , Rosowsky , A. , Henner , W. D. and Frei , E. , III.Characterization of a human squamous carcinoma cell line resistant to cis‐diamminedichloroplatinum(II) . Cancer Res. , 47 , 388 – 393 ( 1987. ). [PubMed] [Google Scholar]
  • 3. ) Ishikawa , T. and Ali‐Osman , F.Glutathione‐associated cis‐diamminedichloroplatinum(II) metabolism and ATP‐dependent efflux from leukemia cells. Molecular characterization of glutathione‐platinum complex and its biological significance . J. Biol. Chem. , 268 , 20116 – 20125 ( 1993. ). [PubMed] [Google Scholar]
  • 4. ) Mannervik , B. , Alin , P. , Guthenberg , C. , Jensson , H. , Tahir , M. K. , Warholm , M. and Jörnvall , H.Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties . Proc. Natl. Acad. Sci. USA , 82 , 7202 – 7206 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Tsuchida , S. and Sato , K.Glutathione transferases and cancer . Crit. Rev. Biochem. Mot Biol , 27 , 337 – 384 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Kodate , C. , Fukushi , A. , Narita , T. , Kudo , H. , Soma , Y. and Sato , K.Human placental form of glutathione S‐transferase (GST‐II) as a new immunohistochemical marker for human colonic carcinoma . Jpn. J. Cancer Res. (Gann) , 77 , 226 – 229 ( 1986. ). [PubMed] [Google Scholar]
  • 7. ) Hatayama , I. , Nishimura , S.Narita , T. and Sato , K.Sex‐dependent expression of class pi glutathione S‐transferase during chemical hepatocarcinogenesis in B6C3F1 mice . Carcinogenesis , 14 , 537 – 538 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Batist , G. , Behrens , B. C. , Makuch , R. L. , Hamilton , T. C. , Katki , A. G. , Louie , K. G. , Meyers , C. E. and Ozols , R. F.Serial determinations of glutathione levels and glutathione‐related enzyme activities in human tumor cells in vitro . Biochem. Pharmacol , 35 , 2257 – 2259 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Saburi , Y. , Nakagawa , M. , Ono , M. , Sakai , M. , Muramatsu , M. , Kohno , K. and Kuwano , M.Increased expression of glutathione S‐transferase gene in cis‐diamminedichloroplatinum(II)‐resistant variants of a Chinese hamster ovary cell line . Cancer Res. , 49 , 7020 – 7025 ( 1989. ). [PubMed] [Google Scholar]
  • 10. ) Hamilton , T. C. , Winker , M. A. , Louie , K. G. , Batist , G. , Behrens , B. C. , Tsuruo , T. , Grotzinger , K. R. , Mckoy , W. M. , Young , R. C. and Ozols , R. F.Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drugresistant and sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion . Biochem. Pharmacol , 34 , 2583 – 2586 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Tew , K. D. , Bomber , A. M. and Hoffman , S. J.Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines . Cancer Res. , 48 , 3622 – 3625 ( 1988. ). [PubMed] [Google Scholar]
  • 12. ) Awasthi , S. , Sharma , R. , Singhal , S. S. , Herzog , N. K. , Chaubey , M. and Awasthi , Y. C.Modulation of cisplatin cytotoxicity by sulphasalazine . Br. J. Cancer , 70 , 190 – 194 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Sakai , M. , Okuda , A. and Muramatsu , M.Multiple regulatory elements and phorbol 12‐O‐tetradecanoate 13‐acetate responsiveness of the rat placental glutathione transferase gene . Proc. Natl Acad. Set. USA , 85 , 9456 – 9460 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Okuda , A. , Imagawa , M. , Sakai , M. and Muramatsu , M.Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells . EMBO J. , 9 , 1131 – 1135 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Xu , X. and Stambrook , P. J.Two murine GSTpi genes are arranged in tandem and are differentially expressed . J. Biol. Chem. , 269 , 30268 – 30273 ( 1994. ). [PubMed] [Google Scholar]
  • 16. ) Sakai , M.Okuda , A. , Hatayama , I. , Sato , K. , Nishi , S. and Muramatsu , M.Structure and expression of the rat c‐jun messenger RNA: tissue distribution and increase during chemical hepatocarcinogenesis . Cancer Res. , 49 , 5633 – 5637 ( 1989. ). [PubMed] [Google Scholar]
  • 17. ) Hatayama , I. , Yamada , Y. , Tanaka , K. , Ichihara , A. and Sato , K.Induction of glutathione S‐transferase P‐form in primary cultured rat hepatocytes by epidermal growth factor and insulin . Jpn. J. Cancer Res. , 82 , 807 – 814 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Nakano , H. , Hatayama , I. , Satoh , K. , Suzuki , S. , Sato , K. and Tsuchida , S.c‐Jun expression in single cells and preneoplastic foci induced by diethylnitrosamine in B6C3F1 mice: comparison with the expression of pi‐class glutathi one S‐transferase . Carcinogenesis , 15 , 1853 – 1857 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Imagawa , M. , Osada , S. , Koyama , Y. , Suzuki , T. , Hirom , P. C. , Dicciani , M. B. and Muramatsu , M.SF‐B that binds to a negative element in glutathione transferase P gene is similar or identical to trans‐activator LAP/IL6‐DBP . Biochem. Biophys. Res. Commun. , 179 , 293 – 300 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Poli , V. , Mancini , F. P. and Cortese , R.IL‐6DBP, a nuclear protein involved in interleukin‐6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP . Cell , 63 , 643 – 653 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Strassmann , G. , Jacob , C. O. , Evans , R. , Beall , D. and Fong , M.Mechanisms of experimental cancer cachexia. Interaction between mononuclear phagocytes and colon‐26 carcinoma and its relevance to IL‐6‐mediated cancer cachexia . J. Immunol. , 148 , 3674 – 3678 ( 1992. ). [PubMed] [Google Scholar]
  • 22. ) Chihara , G. , Maeda , Y. , Hamuro , J. , Sasaki , T. and Fukuoka , F.Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) Sing . Nature , 222 , 687 – 688 ( 1969. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Sasaki , T. , Takasuka , N. , Chihara , G. and Maeda , Y. Y.Antitumor activity of degraded products of lentinan: its correlation with molecular weight . Gann , 67 , 191 – 195 ( 1976. ). [PubMed] [Google Scholar]
  • 24. ) Zakany , J. , Chihara , G. and Fachet , J.Effect of lentinan on tumor growth in murine allogeneic and syngeneic hosts . Int. J. Cancer , 25 , 371 – 376 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Maeda , Y. Y. , Chihara , G. and Ishimura , K.Unique increase of serum proteins and action of antitumor polysaccharides . Nature , 252 , 250 – 252 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Suga , T. , Maeda , Y. Y. , Uchida , H. , Rokutanda , M. and Chihara , G.Macrophage‐mediated acute‐phase transport protein production induced by lentinan . Int. J. Immuno-pharmacoL , 8 , 691 – 699 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Tanaka , Y. , Eda , H. , Tanaka , T. , Udagawa , T. , Ishikawa , T. , Horii , I. , Ishitsuka , H. , Kataoka , T. and Taguchi , T.Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice . Cancer Res. , 50 , 2290 – 2295 ( 1990. ). [PubMed] [Google Scholar]
  • 28. ) Ahmed , S. A. , Gogal , R. M. , Jr. and Walsh , J. E.A new rapid and simple non‐radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to 3H‐thymidine incorporation assay . J. Immunol. Methods , 170 , 211 – 224 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Habig , W. H. , Pabst , M. J. and Jakoby , W. B.Glutathione S‐transferases. The first enzymatic step in mercapturic acid formation . J. Biol. Chem. , 249 , 7130 – 7139 ( 1974. ). [PubMed] [Google Scholar]
  • 30. ) Lowry , O. H. , Rosebrough , N. J. , Farr , A. L. and Randall , R. J.Protein measurement with the Folin phenol reagent . J. Biol Chem. , 193 , 265 – 275 ( 1951. ). [PubMed] [Google Scholar]
  • 31. ) Owens , C. W. and Belcher , R. V.A colorimetric micromethod for the determination of glutathione . Biochem. J. , 94 , 705 – 711 ( 1965. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. ) Soma , Y. , Satoh , K. and Sato , K.Purification and subunit structural and immunological characterization of five glutathione S‐transferases in human liver, and the acidic form as a hepatic tumor marker . Biochim. Biophys. Acta , 869 , 247 – 258 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) O'Farrell , P. H.Higher resolution two‐dimensional electrophoresis of proteins . J. Biol. Chem. , 250 , 4007 – 4021 ( 1975. ). [PMC free article] [PubMed] [Google Scholar]
  • 34. ) Tsuchida , S. , Izumi , T. , Shimizu , T. , Ishikawa , T. , Hatayama , I. , Satoh , K. and Sato , K.Purification of a new acidic glutathione S‐transferase, GST‐Yn1 Yn1, with a high leukotriene‐C4 synthase activity from rat brain . Eur. J. Biochem. , 170 , 159 – 164 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 35. ) Hatayama , I. , Satoh , K. and Sato , K.Developmental and hormonal regulation of the major form of hepatic glutathi‐one S‐transferase in male mice . Biochem. Biophys. Res. Commun. , 140 , 581 – 588 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 36. ) Tateoka , N. , Tsuchida , S. , Soma , Y. and Sato , K.Purification and characterization of glutathione S‐transferases in human kidney . Clin. Chim. Acta , 166 , 207 – 218 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 37. ) Nakagawa , K. , Saijo , N. , Tsuchida , S. , Sakai , M. , Tsunokawa , Y. , Yokota , J. , Muramatsu , M. , Sato , K. , Terada , M. and Tew , K. D.Glutathione‐S‐transferase as a determinant of drug resistance in transfectant cell lines . J. Biol. Chem. , 265 , 4296 – 4301 ( 1990. ). [PubMed] [Google Scholar]
  • 38. ) Laemmli , U. K.Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature , 227 , 680 – 685 ( 1970. ). [DOI] [PubMed] [Google Scholar]
  • 39. ) Towbin , H. , Staehelin , T. and Gordon , J.Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications . Proc. Natl. Acad. Sci. USA , 76 , 4350 – 4354 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. ) Siddik , Z. H. , Boxall , F. E. and Harrap , K. R.Flameless atomic absorption spectrophotometric determination of platinum in tissues solubilized in hyamine hydroxide . Anal. Biochem. , 163 , 21 – 26 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 41. ) Mizutani , Y. , Bonavida , B. , Koishihara , Y. , Akamatsu , K. , Ohsugi , Y. and Yoshida , O.Sensitization of human renal cell carcinoma cells to cis‐diamminedichloroplatinum (II) by anti‐interleukin 6 monoclonal antibody or anti‐interleukin 6 receptor monoclonal antibody . Cancer Res. , 55 , 590 – 596 ( 1995. ). [PubMed] [Google Scholar]
  • 42. ) Descombes , P. and Schibler , U.A liver‐enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA . Cell , 67 , 569 – 579 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 43. ) Ishikawa , T. , Wright , C. D. and Ishizuka , H.GS‐X pump is functionally overexpressed in cis‐diamminedichloroplatinum(II)‐resistant human leukemia HL‐60 cells and down‐regulated by cell differentiation . J. Biol. Chem. , 269 , 29085 – 29093 ( 1994. ). [PubMed] [Google Scholar]
  • 44. ) Eastman , A. and Schulte , N.Enhanced DNA repair as a mechanism of resistance to cis‐diamminedichloroplatinum (II) . Biochemistry , 27 , 4730 – 4734 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 45. ) Zhen , W. , Link , C. J. , Jr. , O'Connor , P. , Reed , E. , Parker , R. , Howell , S. and Bohr , V.Increased gene‐specific repair of cisplatin interstrand cross‐links in cisplatin‐resistant human ovarian cancer cell lines . Mol. Cell Biol. , 12 , 3689 – 3698 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. ) Zaman , G. J. R. , Lankelma , J. , van Tellingen , O. , Beijnen , J. , Dekker , H. , Paulusma , C. , Oude Elferink , R. P. , Baas , F. and Borst , P.Role of glutathione in the export of compounds from cells by the multidrug‐resistance‐associated protein . Proc. Natl. Acad. Sci. USA , 92 , 7690 – 7694 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. ) Kuzmich , S. , van Der Veer , L. A. , Walsh , W. S. , Lacreta , F. P. and Tew , K. D.Increased levels of glutathione S‐transferase‐π as a mechanism of resistance to ethacrynic acid . Biochem. J. , 281 , 219 – 224 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES