Anticancer Effects of a Tertiary Sulfonium Compound, Dimethylsulfoniopropionate, in Green Sea Algae on Ehrlich Ascites Carcinoma-Bearing Mice

Abstract

SummaryThe saline and dimethylsulfoniopropionate (DMSP) solutions at 5, 10 and 20 m M were preliminarily injected intraperitoneally every other day into two control and three DMSP groups of mice ( n ϭ 8) for 2 wk and thereafter Ehrlich ascites-carcinoma (EAC) cells were peritoneally injected to one control and three DMSP groups of mice, leaving one control group without the EAC injection. Then, the body weight and survival time of all mice were examined over a long rearing time up to 300 d. All EAC-bearing mice, especially the carcinoma control and 5 m M DMSP-carcinoma group mice, rapidly increased their body weights early and then died by day 50 and day 90, respectively. In contrast, the administration of 10 and 20 m M DMSP solutions prolonged the lives of EAC-bearing mice at the survival rate of 50 and 63% respectively up to 300 d without any side effects. Furthermore, the administration of 10 m M DMSP solution proved to activate the delayed-type hypersensitivity of EAC bearing-mice, and the DMSP solutions over the concentrations of 5 to 30 m M to slightly reduce the dead cells in EAC cells on the synthetic medium. Accordingly, the preliminary supplementation of 10 and 20 m M DMSP solutions to EAC-bearing mice was proven to maintain their lives at high survival rates without direct damage to EAC cells for a long time, probably due to the activation of the immune system without any side effects. Key Words dimethylsulfoniopropionate, Ehrlich ascites carcinoma, survival time, DTH reaction A tertiary sulfonium compound, dimethylsulfoniopropionate (DMSP), proves to be naturally synthesized and contained in large amounts in green sea algae ( 1 , 2 ) and sea plankton ( 3 ) and to be distributed to various aquatic animals ( 1 ). Therefore, DMSP has been habitually ingested in large and small amounts around the world, especially in Japan for a long time ( 4 ). However, there is no report on research into the physiological role of DMSP except for compatible solutes (osmoregulant, cryoprotectant ( 3 , 5 )) although there are a number of reports concerning its metabolism in micro-, macroalgae and halophytic plants ( 6 ). We therefore have examined the effects of DMSP and related compounds on a number of diseased animals, which have verified that the compound ameliorates and/or mitigates a variety of diseases, especially serious comtemporary disorders: stress-induced gastric ulcers in rats ( 7 ), acute alloxan-diabetes mellitus in rats ( 8 ), hyperhomocysteinemia ( 9 , 10 ), early aging and loss of learning and memory in SAM-R1 and -P8 (Alzheimer's disease) ( 11 , 12 ), 3 ′ -methyl-4-dimethylamino-azobenzene-(3 ′ -MeDAB)-induced liver cancer in rats ( 13 ) and Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice ( 14 ) and SAMP8 ( 15 ). Moreover, the amelioration of the early aging and loss of learning and memory in SAMP8 was confirmed by experiments with diets containing 5% of pulverized dry green sea algae ( 16 ).In contrast, other naturally occurring-sulfonium compounds, dimethylsulf...

Carcinoma Infection and Immune Systems of Ehrlich Ascites Carcinoma-Bearing Mice Treated with Structurally Similar Sulfonium Compounds

“…Recently we found that oral supplementation with 10 mM DMSP solution nearly reinstated 3 0 -methyl-4-dimethylaminoazobenzene (3 0 -MeDAB)-induced liver cancers in rats at the 33rd week, 9) and that intraperitoneal (ip) administration of 10 and 20 mM DMSP solutions to Ehrlich ascites carcinoma (EAC)-bearing mice maintain high survival rate (50 and 63%) for up to 300 d without side effect. 10) In these experiments, DMSP was found to activate the delayed-type hypersensitive immune system in the cancerous animals. 9,10) Hence a comparison of the effects of DMSA, DMSP and MeMet (Fig.…”

“…10) In these experiments, DMSP was found to activate the delayed-type hypersensitive immune system in the cancerous animals. 9,10) Hence a comparison of the effects of DMSA, DMSP and MeMet (Fig. 1A) on the carcinoma and the immune systems in EAC-bearing mice was made in this study.…”

“…The test compounds were supplemented only once for the start of the experiments. The amounts of DMSP in 0.5 mL of the 10 mM DMSP solution corresponded to the amounts of DMSP in dry green sea algae (about 2.5-5 g), 10) being possibly available amounts per day per person. The results obtained represent that the body weights which subtracted the ascites volumes (g) from the body weight in each group were 40:0 AE 5:0, 37:2 AE 3:5, 39:0 AE 1:7, and 43:3 AE 4:9 g (means AE SD, n ¼ 8) for the Carcinoma-Control, -DMSA, -DMSP, and -MeMet groups on the 10th day, being the same values as those (39:7 AE 3:0 g (means AE SD, n ¼ 8)) for the control group, without statistical differences (p < 0:05) among them.…”

“…Then dead cells were counted in a Neubauer hematocytometer using trypan blue dye and expressed in terms of the ratios (%) (means AE SD, n ¼ 5) of dead cells versus all the EAC cells in a given group. 10) Care and treatment of the experimental animals was approved by the Experimental Animal Committee of the Faculty of Nutrition of Koshien University. Statistical analysis and determination of the two-dimensional structures of the test compounds were performed using ANOVA and the Tukey-Kramer test and CSC ChemDraw (StatView-SAS Institute, version 5 and Cambridge Scientific Computing, version 3.1) respectively.…”

“…2.1.1.3] to form methionine from homocysteine in animals 4) and recently, as a secondary osmoregulant in bacteria and sea algae, 5) DMSP is recognized as a representative osmolyte in marine organisms, 2) a potent methyl group donor, 6) and a healing compound for various diseased animals, in our previous experiments. [7][8][9][10] MeMet, which is synthesized in a number of plants, 11) is known as an anti-gastric ulcer agent in animals and humans, 5,7) and also as a methyl-group donor in animals. 6) Cancer continues to spread and demonstrates the high mortality rate in the world to date for humans.…”