Abstract
The liquid from heat-treatment of an abalone, Haliotis discus hannai, which is normally discarded as waste, was found to contain a new glycoprotein antineoplastic agent. A fraction of the liquid obtained from chromatography that was 22% carbohydrate and 44% protein was injected locally or systematically into ICR mice or BALB/c mice inoculated s.c. with allogeneic sarcoma 180 or syngeneic Meth-A fibrosarcoma, and growth of the tumors was strongly inhibited. There was an optimum dose range for the inhibition of the growth of sarcoma 180, and optimum timing. The fraction did not have antitumor activity in T cell-deficient nude mice (CD-1 nu/nu or BALB/c nu/nu mice), and administration of carrageenan in vivo decreased its activity in ICR mice. This fraction activated the cytostatic activity of peritoneal and alveolar macrophages in vivo. These results suggest that the antitumor activity is not due to a direct toxic effect but to stimulation of a host-mediated response.
Keywords: Sarcoma, Nude Mouse, Antitumor Activity, Water Extract, Optimum Timing
References
- 1.Alexander P, Evans R, Grant CK. The interplay of lymphoid cells and macrophages in tumor immunity. Ann Inst Pasteur. 1972;122:645. [PubMed] [Google Scholar]
- 2.Alpenfels WF. A rapid and sensitive method for the determination of monosaccharides as their dansyl hydrazones by high-performance liquid chromatography. Anal Biochem. 1981;114:153. doi: 10.1016/0003-2697(81)90466-8. [DOI] [PubMed] [Google Scholar]
- 3.Dubois M, Gills KA, Hamilton JK, Reberts PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem. 1956;28:350. [Google Scholar]
- 4.Hamuro J, Chihara G. Lentinan, a T-cell-oriented immunopotentiator: its experimetal and clinical applications and possible mechanism of immune modulation. In: Fenichel RL, Chirigos MA, editors. Immune modulation agents and their mechanisms. New York: Marcel Dekker, Inc; 1984. p. 409. [Google Scholar]
- 5.Howard JG, Christe GH, Book JL, Kinsky PG. Peritoneal and alveolar macrophages derived from lymphocyte population during graft-versus-host reaction. Br J Exp Pathol. 1972;50:448. [PMC free article] [PubMed] [Google Scholar]
- 6.Ito M, Iizuka H, Masuno T, Yasunari R, Ogura T, Yamamura Y. Killing of tumor cells in vitro by macrophages from mice given injections of squalene-treated cell wall skelton of Nocardia rubra . Cancer Res. 1981;41:2925. [PubMed] [Google Scholar]
- 7.Kumagai K, Itoh K, Hinuma S, Tada M. Pretreatment of plastic Petri dishes with fetal calf serum. A simple method for macrophage isolation. J Immunol Methods. 1977;29:17. doi: 10.1016/0022-1759(79)90121-2. [DOI] [PubMed] [Google Scholar]
- 8.Li CP, Goldin A, Hartwell JL. Antineoplastic substances from the sea: A review. Cancer Chemother Rep. 1974;4:97. [PubMed] [Google Scholar]
- 9.Lowry OH, Rosebrough NJ, Farr AL, Randall RL. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265. [PubMed] [Google Scholar]
- 10.Mopper K, Johnson L. Reversed-phase liquid chromatographic analysis of Dns-sugars. Optimization of derivatization and chromatographic procedures and applications to natural samples. J Chromatogr. 1983;256:27. [Google Scholar]
- 11.Muramoto K, Kamiya H. Analyses of dansyl and dabsyl amino acids by reversed-phase high-performance liquid chromatography. Bull Japan Soc Sci Fish. 1985;51:817. [Google Scholar]
- 12.Ohki M, Nakamura T, Morita T, Iwanaga S. A new endotoxin sensitive factor associated with hemolymph coagulation system of horseshoe carb (Limulidae) FEBS Lett. 1980;120:217. doi: 10.1016/0014-5793(80)80301-2. [DOI] [PubMed] [Google Scholar]
- 13.Sasaki T, Tanaka M. Antimacrophage agents decreased the antitumor effect of water-soluble carboxymethylated (1–3)-β-D-glucan. Eur J Cancer. 1980;16:1271. doi: 10.1016/0014-2964(80)90188-7. [DOI] [PubMed] [Google Scholar]
- 14.Sasaki T, Takasuka N, Abiko N. Antitumor activity of a boiled scallop extract. J Natl Cancer Inst. 1978;60:1499. doi: 10.1093/jnci/60.6.1499. [DOI] [PubMed] [Google Scholar]
- 15.Sasaki T, Tanaka M, Uchida H. Effect of serum from mice treated with antitumor polysaccharide on expression of cytotoxicity by mouse peritoneal macrophages. J Pharmacobio-Dyn. 1982;5:1012. doi: 10.1248/bpb1978.5.1012. [DOI] [PubMed] [Google Scholar]
- 16.Sasaki T, Uchida NA, Uchida H, Takasuka N, Kamiya H, Endo Y, Tanaka M, Hayashi T, Shimizu U. Antitumor activity of aqueous extracts of marine animals. J Pharmacobio-Dyn. 1985;8:969. doi: 10.1248/bpb1978.8.969. [DOI] [PubMed] [Google Scholar]
- 17.Sasaki T, Uchida H, Uchida NA, Tachibana Y, Nakamichi K, Takasuka N, Endo Y (1986) Antitumor activity and immunomodulatory effect of glycoprotein fraction from scallop, Patinopecten yessoensis. Bull Japan Soc Sci Fish, in press
- 18.Suga T, Shiio T, Maeda YY, Chihara G. Antitumor activity of lentinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3-methylcholanthrene-induced carcinogenesis. Cancer Res. 1984;44:5132. [PubMed] [Google Scholar]
- 19.Uchida H, Sasaki T. Comparative study of antitumor activity and immunomodulatory effect of tetrahydro-2-furnayl and tetrahydro-2-pyranyl (1 → 3)-β-D-glucans. J Pharmacobio-Dyn. 1983;6:660. doi: 10.1248/bpb1978.6.660. [DOI] [PubMed] [Google Scholar]
- 20.Whistler RL, Bushway AA, Singh PP, Nakahara W, Tokuzen R. Noncytotoxic, antitumor polysaccharides. Adv Carbohydr Chem Biochem. 1976;32:235. doi: 10.1016/s0065-2318(08)60338-8. [DOI] [PubMed] [Google Scholar]