Abstract

620

A novel fermented soy supplement, Yang Zhenhua 851, has been safely and successfully used for about 20 years in China, USA and other countries as sole mainstay treatment or as adjuvant nutrition to treat cancer patients. It has been found that the unique branched chain fatty acids in fermentation broth, 12 methyltetradecanoic acid (12MTD) and 13 methyltetradecanoic acid (13MTD), played important role in anticancer benefits, which were from used bacteria membrane’s metabolites. In order to increase the anticancer activity, a series of structurally modified derivatives have been synthesized. Here some recent in vivo tests on 12MTD and one of 13MTD’s derivatives, D79, will be presented, including subacute and acute toxicity studies and efficacy tests to inhibit tumor growth in mouse cervical cancer U₁₄ model. In the tests on 12MTD two different animal models were compared, i.e. intraperitoneal (ip) and intragastric (ig) administration. In subacute toxicity test, 20 mice of same in each gender were given with ip injection of daily dose 0.3 ml/10g of 1% 12MTD, and another 20 mice with ig of 1 ml/10g of 5% 12MTD, for 10 days to observe the response. On the other hand, in acute toxicity test, only once administration was given and followed by 7 days continuing observation, with ip dose 0.3 ml/10g of 1% 12MTD or ig dose 0.5 ml/10g of 5% 12MTD, respectively. No death was found in all observations, suggesting that LD50 (ip) is over 900 mg/kg, and LD50 (ig) is over 7.5 g/kg, respectively. The results of efficacy of 12MTD in mouse cervical cancer U₁₄ model indicated that either ip administration in daily dose of 200 mg/kg 12MTD or ig administration in 2 g/kg for 10 days significantly inhibited the tumor growth. The inhibition rate is 56.96% (p<0.001) in ip model and 52.06% (p<0.05) in ig model, respectively, indicating that ip dose is about 1/10 of ig dose in similar effects. The parallel tests were conducted for compound D79, one of 13MTD’s derivatives, suggesting that structurally modified derivative had possessed more potent anticancer activity. The results showed that the ip administration in daily dose of 10 mg/kg D79 for 10 days significantly inhibited the tumor growth in mouse cervical cancer U₁₄ model, with inhibition rate of 46.72% (p<0.05). This effective dose is much lower than that of 12MTD, and is only 1/3 of that of a standard chemotherapeutic drug, Cytoxan. The subacute toxicity test on D79 showed that ip injection induced irritative response, but 10 days continuing administration of daily dose 5 - 15 mg/kg did not induce any death. Based on Bliss method, the acute toxicity tests on ip D79 determined LD50 (ip)about 24.54 mg/kg.