ANTITUMOR ACTIVITY OF A POLYSACCHARIDE PREPARATION FROM MARINE BACTERIA
Koichi OKUT'ANI
A Gram-negative, rod shaped bacterium, strain No 11-15, isolated from marine envir on- ment produced the viscous substances in the culture media") It was shown that a white polymer positive in the anthrone and phenol-sulfuric acid test was recovered from the viscous fermentation broth by precipitation with acetone
The author found antitumor activity in this preparation The polysaccharide preparations from many origin are known to exhibit interesting biological activities such as an antitumor a c t i v i t ~ ~ ' - " ~ ' ~ h e present short communication is concerned with the antitumor activity of this material
The isolation procedure of this preparation was shown in Fig 1
Marine bacterium No1 1 - 15
ZoBell 2216E liquid media(''' at 15-20°C for a week Centrifugation SUP
I
%%acetone Filtrationresprot
water filtrate ~ i l t i a t ion t residue filtrate I Filtration I residue filtr'ate 1(
hot water residue 1Dialysis against water 1
1 Lyophilizing
I
white powder
Fig 1 Isolation procedures of a polysaccharide preparation from marine bacterium No 11 - 15,
76 Tech. Bull. Fac.. Agr.. Kagawa Univ.
As shown in Fig 1, the procedure consists of precipitation with acetone The lyophilized materials were white powder yielding 1-2 g per liter culture fluid, and were easily soluble in water
Female mice (ddY) weighing about 20 g were used for the antitumor assay Sarcoma- 180 (ascites type) were injected itraperitoneally, and Nakahara-Fukuoka sarcoma (NF-sar- coma, solid type) subcutaneously
Drugs were intraperitoneally or subcutaneously injected daily for 5 days The results obtained were shown in Table 1
As shown in Table 1, the preparation had good antitumor activity This activity ratio was compared with that in Mitomycin-C In the intraperitoneal injection of 0 10 mg/Kg/day x5 of this material, the growth of mouse ascites carcinoma was inhibited at the ratio of 60 per cent, and 1 0 0 mg/Kg/day x5, 84 per cent On the contrary, 50 per cent inhibition was found in the subcutaneous injection in doses of 25 mg/Kg/day x5
Table 1 Antitumor activity of a polysaccharide preparation from marine bacterium NO 11-15
Sarcoma- 180 NF-sarcoma
,
Drug Dose Route Tumor growth Inhibition Tumor growth Inhibition
mg/Kg/day T/C % ac t i v ~ ty
--
T / C % 1 activity 0 10 i P 38 7++
/ / Sample 0 50 i P 28 9++
/ / 1 00 I P 16 4++
/ / 5.00 I P 12 4--
++ /--
- / 5 00 s c 96 1 / / 25.00 s c 52 6+
/ /-
25 00 i P / . / 94 2-
50.. 00 i. p.-
-
/ / 59. 7+
0. 10 i. p. 57.. 7+
/ / Mitomycin- C 0.. 20 i..p. 19. 7++
/ / 1.. 00 i, p.. 1 / 28.. 6++
the mean value of treated group The tumor growth T/C % :
that of control X 100
The inhibition activity: Sarcoma-180 T/C %, 100-66 (-) 65-41 (+) 40-11 (f f ) 10-0 (+++I NF-sarcoma T/C %, 100-71 (-) 70-51 (+) 50-21 (+ +) 20-0 (+++I
The data show that antitumor activity of this material varied according to the route of injection
In doses of 50 mg/Kg/day x5, only 40 per cent inhibition was found in NF-sarcoma The LDSc value of this material in mice was 200-300 mg/Kg i p
References
(1) OKUTANI, K : ibst Ann Meet J U ~ SOC S L L Cuncl,r Ihp 23, 201 (1963)
F~sh , p 531 (1973) (4) SAKAI, S , SAITO,G, SUGAYAMA,T, TAKANO, T ,
(2) BRADNER, W T , CLARK, D A , STOCK, C C : TAKEDA, S : 55, 197 (1964)
Cancer Res , 18, 347 (1958) (5) NAKAHARA, W , FUKUOKA, F , MAEDA, Y , AOKI,
(3) DILLER, I C , MANKOWSKI, Z T , FISHER, M E : K : Gann 55, 283 (1964)
OLIVE 香川大学学術情報リポジトリ
Vol.. 26, No.. 1 (1974)
(13) K o ~ A r s u , N , O K U B O , ~ , KIKUMOTO, S , KIMURA, K , SAITO, G , SAKAI, S : Gorzn, 60, 137 (1969)
(14) SUZUKI, S , SUZUKI, M , HATSUKAINA, H , S U N A YAMA, H , SUZUKI, T , UCHIYAMA, M , FUKUOKA, F , NAKANISHI, M , AKIYA, S : ( ; c ~ n r ~ , 60, 273 (1969)
(15) CHIHARA , G , MAEDA, Y , ~ H A M U R O , J , SASAKI, T ,
FUKUOKA, F : N ~ L L I L I P , 222, 687 (1969)
(16) IKEKAWA,T, M A E D A , ~ , UEHARA, N , NAKANISHI, M , FUKUOKA, F : ( n n t r r Rrs 29, 734 ( 1969) (17) Horo, H , UCHIYAMA, M , SUZUKI, S : Y c ~ k u g ( ~ k ~ .
Z L S S ~ L , 93, 947 (1973)
(18) O P P E N H E I M E R , C H : S y r n ~ ) o > ~ n r n or1 M u r ~ n r M ~ c r o b ~ o l o g y , p 596 ,,Charles C Thomas Publisher, U S A (1963)
Z
t 5a
g#f$f$h'&f&lL$'j ' T ~ ~ 4 a ~ . ~ . $ ~ ~ l ~ l ~ & i ~ < ' $ 2 & j ~ ' & $ ( %[]&$L.T& '1, ~ ~ ~ ~ ~ @ $ ) J T ~ ~ ~ $ ~ J T ~ ~ [ & T & I % $ $ E ( $ I Z M
T&$jfRIi@!NitL ,L2)-1'7)
~ ~ l i f ~ j ~ : $ ~ ~ ~ ~ - ~ ~ ~ j 1 ~ ! # . ~ - ~ ~ $ & ~ ~ i ~ ~ h ~ $ # ) ~ j f $ ~ h ~ : ~ & ~ b ~ $ ~ ~ ~ ~ 1 : ~ ~ ' &$k.Tli, :n%$'ihj-?97,Sar- coma-1801:B.f L T T ( k ~ l : l ~ ~ f i k t ~ l J $ l ] $ j ~ ~ $ iliT2 !: 1 : - 3 ~ > T G 7 4 h .
j b ~ ~ ~ : : 9 i l ~ i N o l 1 - 1 5 ~ ~ ~ ~ ~ 0 Fig 1 l;ij<$ Ij&i: ,jk 1) +&,'i: L 1: %$EfC& 4Q71<1L:i&h~LddY$:~?.f X,?'Grt:%& 475 -? 1:.
-?a$$%liTable 1 k:rl<-b t $5 I) T A b 8 .
Sarcoma - 18Oo)JJ%;lkHI~11:tJ L 7 t i 0 lOmg/kg/day ,, 5 DJJkll!:rt;l4~4 2 b: V 1 OOmg/kg/day
.
5 aHEnPrf;l.&'ii Ti;, ?AT $tllYdC?l'qfib & -?kL?kL6O%$j k84%fllJ$l] L h . 5 1) & ; L > ~ A 14i& ir< L 1 ~ , L ~ J , L ChjhjB-Cj )$#& I&-\. 1:'&2 f:f$j&o)PIJ %llj$lf 25mg/kg/day ,, 5 Tt
50%T h 5. - h , 1&1 fi31G 7 $I 5 NF-Sarcomat: BfL
.T I t , 50mg/kg/day.
5 EJJB+ - T 4 0 % l J l ] 1 : C ?' 7 4 , Li!l$$Aj;hkVtg
$$.E%O$L!%l: b: ') ?C?Eiii#$4gii3'l%lt2i1L ( {~1-[;'+5 Z !: + ~ ~ 8 h ~ k ~ l : , !'i$j~G7)&&$hOL.Dso Ii?37\Jl2,ll!~?lf;I%$ (24~+tiHq) T 200 --300mg/kgT h .-? 1:.
(Received May 31, 1974)
