Inhibition of chemically induced carcinogenesis by drugs used in homeopathic medicine.

Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental animals. Presently we have evaluated the inhibitory effects of potentized homeopathic preparations against N'-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in rats as well as 3-methylcholanthrene-induced sarcomas in mice. We have used Ruta, Hydrastis, Lycopodium and Thuja, which are commonly employed in homeopathy for treating cancer. Administration of NDEA in rats resulted in tumor induction in the liver and elevated marker enzymes such as gamma-glutamyl transpeptidase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase in the serum and in liver. Concomitant administration of homeopathic drugs retarded the tumor growth and significantly reduced the elevated marker enzymes level as revealed by morphological, biochemical and histopathological evaluation. Out of the four drugs studied, Ruta 200c showed maximum inhibition of liver tumor development. Ruta 200c and phosphorus 1M were found to reduce the incidence of 3-methylcholanthrene-induced sarcomas and also increase the life span of mice harboring the tumours. These studies demonstrate that homeopathic drugs, at ultra low doses, may be able to decrease tumor induction by carcinogen administration. At present we do not know the mechanisms of action of these drugs useful against carcinogenesis.

Cancare-a herbal formulation inhibits chemically induced tumours in experimental animals.

Cancer chemopreventive potential of Cancare, a multi-herbal formulation on chemically induced tumours was studied by N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats and 20-methylcholanthrene (20-MC) induced sarcoma development in mice. Oral administration of Cancare was found to inhibit the liver tumour development induced by N-nitrosodiethylamine. Animals administered with NDEA had visible liver tumours by the end of 30th weeks and the liver weight was raised to 6.1 +/- 1.4 g/ 100 g body wt. None of the animals treated with Cancare (150 mg/ kg) developed any visible liver tumours by this period and the liver weight was 3.0 +/- 0.6 g/ 100 g body wt. Gamma-Glutamyl transpeptidase, a marker of hepatocellularcarcinoma, which was raised to 83.7 +/- 8. 9 U/l in serum of NDEA treated group was reduced to 35.2 +/- 6.1 U/l by simultaneous administration of Cancare. Elevated levels of serum alkaline phosphatase, glutamate pyruvate transaminase, bilirubin, liver glutathione S-transferase, glutathione and gamma-Glutamyl transpeptidase in the NDEA administered group was significantly reduced by Cancare administration. Cancare administration inhibited the sarcoma development and increased the life span of mice administered with 20-MC dose dependently. All animals in the control group developed sarcomas by 150th day and dead by 174th day after 20-MC administration. Cancare administration (30 mg and 150 mg/kg) inhibited the sarcoma development (46.7 and 60%) as well as increased the life span (53.3 and 66.7%) as estimated on 240th day after 20-MC administration. The results are indicative of the chemopreventive potential of Cancare against chemically induced neoplasmas.

Antioxidant and anticarcinogenic activity of Lycovin--an indigenous herbal preparation.

Aqueous extract of Lycovin has been found to be a potent inhibitor of lipid peroxide formation, (IC50 = 500 micrograms/ml) and scavenger of hydroxyl radical (IC50 = 44 micrograms/ml) and superoxide radical (IC50 = 30 micrograms/ml) in vitro. Lycovin syrup 1.5 ml and 7.5 ml/kg body wt administered orally, reduced the development of sarcoma induced by 20 MC by 35% and 70% respectively. Lycovin syrup was also found to inhibit the hepatocarcinogenesis induced by NDEA. The tumour incidence was 100% in the control group, while none of the drug treated animals developed tumour. Liver weight, gamma-glutamyl transpeptidase (GGT), GSH-S-transferase (GST), reduced glutathione, (GSH) and aniline-4-hydroxylase in liver were elevated in NDEA alone treated animals. The serum parameters indicative of liver injury such as bilirubin, lipid peroxides, alkaline phosphatase and glutamate pyruvate transaminase were also elevated by NDEA administration. These elevated parameters were significantly reduced in animals treated with Lycovin syrup along with NDEA in a dose dependent manner. Even though the exact mechanism of action is not known at present, the observed anticarcinogenic activity may be due to the inhibition of P.450 enzyme activity and subsequent inhibition of the production of the ultimate carcinogen as well as scavenging of oxygen free radicals during promotion of the transformed cell.

Alterations of lipid kinetics and lipoprotein lipase activity in jaundiced tumor bearing rats

Obstructive jaundice is associated with high perioperative morbidity and mortality, and preoperative biliary decompression is still controversial. Profound alterations in intermediary metabolism have been observed with obstructive jaundice. To determine the effect of the common bile duct (CBD) obstruction on lipid metabolism in tumor-bearing animals, free fatty acid (FFA) and very low density lipoprotein-associated triglyceride (VLDL-TG) kinetics were assessed in 20 tumor bearing (subcutaneous MCA sarcoma) Fischer-344 rats, using an obstructive jaundice model. The animals were studied after chronic vascular catheterization, in an unanesthetized, undisturbed state. They were separated into 4 groups: Normal controls (CTL), Tumor-bearing non-jaundiced rats (TBR), Non Tumor Bearing-Jaundiced (NTB-J), Tumor Bearing (tumor burden: 1O per cent body weight)-Jaundiced (TBR-J). All rats were studied 7 days after CBD ligation, or at 1O per cent tumor burden. VLDL-TG and FFA kinetics were assessed by constant infusion of 3H-palmitate-labeled VLDL-TG, and l4C-palmitate bound to albumin, respectively. FFA rate of appearance (FFA-Ra) and clearance (FFA-CI), VLDL-TG rate of appearance (VLDL-TG-Ra) and clearance (VLDL-TG-CI) were determined at steady-states. Tumor burden signiricantly affects FFA-Ra and FFA-CI, as well as VLDL-TG-CI, while CBD ligation selectively affects VLDL-TG-Ra and VLDL-TG-CI. There was significant interaction between tumor burden and jaundice in FFA-Ra. CBD decompression increased significantly VLDL-TG-CI. We conclude that, in jaundiced tumor-bearing rats, tumor burden predominantly affects lipolysis, while CBD obstruction primarily affects triglyceride synthesis and clearance. Lipoprotein lipase (LPL) activity was also markedly decreased by the presence of jaundice and tumor burden, with the associated decrease in the clearance of VLDL-TG.