Homeopathic remedies with antineoplastic properties have immunomodulatory effects in experimental animals.

BACKGROUND: Our previous work suggests that Thuja occidentalis, Carcinosinum and Ruta graveolens have antineoplastic properties. The mechanism of this action has not previously been studied. We studied the hypothesis that the mechanism of action is through the immune modulation. METHODS: We evaluated the effects of Thuja occidentalis, Carcinosinum and Ruta graveolens 1M, 200c and 30c on the immune system of Balb/c mice. The homeopathic preparations were administered orally for ten consecutive days. Haematological parameters (Total White Blood Cell (WBC) Count, Differential Count and Haemoglobin content), haematopoietic parameters (bone marrow cellularity and α-esterase positive cells) and immune parameters for antibody response and lymphoid cell proliferation were assessed using standard methods. Results were analysed by statistical comparison with the control. RESULTS: We observed significant enhancement of haematological parameters including total WBC count, haematopoietic parameters such as bone marrow cellularity and the number of α-esterase positive cells, other parameters of immune response such as circulating antibody titre and the number of plaque forming cells (PFC), particularly with higher dilutions of Thuja and Ruta. Enhanced proliferation of B and T lymphoid cells was also observed. No toxic effects were observed. CONCLUSIONS: The results suggest immunomodulatory activity of homeopathic preparations in high dilution. This may be a mechanism through which homeopathic preparations act.

Effect of homeopathic medicines on transplanted tumors in mice.

Ultra low doses used in homeopathic medicines are reported to have healing potential for various diseases but their action remains controversial. In this study we have investigated the antitumour and antimetastatic activity of selected homeopathic medicines against transplanted tumours in mice. It was found that Ruta graveolens 200c and Hydrastis canadensis 200c significantly increased the lifespan of Ehrlich Ascites Carcinoma and Dalton's Lymphoma Ascites induced tumour-bearing animals by 49.7%, and 69.4% respectively. Moreover there was 95.6% and 95.8% reduction of solid tumour volume in Ruta 200c and Hydrastis 200c treated animals on the 31st day after tumour inoculation. Hydrastis 1M given orally significantly inhibited the growth of developed solid tumours produced by DLA cells and increased the lifespan of tumour bearing animals. Some 9 out of 15 animals with developed tumors were completely tumour free after treatment with Hydrastis 1M. Significant anti-metastatic activity was also found in B16F-10 melanoma-bearing animals treated with Thuja1M, Hydrastis 1M and Lycopodium1M. This was evident from the inhibition of lung tumour nodule formation, morphological and histopathological analysis of lung and decreased levels of gamma-GT in serum, a cellular marker of proliferation. These findings support that homeopathic preparations of Ruta and Hydrastis have significant antitumour activity. The mechanism of action of these medicines is not known at present.

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.

Anti-tumour activity of Ruta graveolens extract.

An extract of Ruta graveolens was found to be cytotoxic to Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and L929 cells in culture (IC100=16 mg/ml) and also to increase the lifespan of tumour bearing animals. The extract further decreased solid tumours developing from DLA and EAC cells when given simultaneously with elongation of the lifespan of tumour-bearing animals. A homeopathic preparation of Ruta graveolens (200 c) was equally effective. Neither was effective for reducing already developed tumours. The Ruta graveolens extract was found to scavenge hydroxyl radicals and inhibit lipid peroxidation at low concentrations. However, at higher concentrations the extract acted as a prooxidant as inhibition of lipid peroxidation and scavenging of hydroxyl radical was minimal. These data indicates that the prooxidant activity of Ruta graveolens may be responsible for the cytocidal action of the extract and its ability to produce tumour reduction.

Induction of apoptosis of tumor cells by some potentiated homeopathic drugs: implications on mechanism of action.

BACKGROUND: Homoeopathic medicines treat diseases, including cancer, using ultradiluted preparations. Earlier studies indicated that homoeopathic medicines are cytotoxic to tumor cells and reduced animal tumors. However, the mechanism of homoeopathic medicines at the cellular level is not known. METHODS: The following drugs were used in the study: Ruta 200C, Carcinosinum 200C, Hydrastis 200C, Thuja 200C, and Thuja 1M. These drugs were tested for their ability to induce apoptosis as seen by morphology, DNA laddering, expression of genes related to apoptosis, and TUNEL assay. Similarly, the effect of homoeopathic medicines on apoptosis was measured by microarray analysis. Activity of Ruta 200C was compared with that of the mother tincture. RESULTS: Ruta 200C produced morphological changes in the Dalton's lymphoma ascites tumor cells and induced DNA laddering. Carcinosinum 200C increased apoptotic gene p53 and Ruta 200C decreased antiapoptotic gene Bcl2. Administration of potentiated homoeopathic drugs to tumor-bearing mice induced TUNEL-positive cells in the tumor, showing increased apoptosis of tumor cells. Microarray analysis of cells treated with homoeopathic drugs indicated that many enzymes related to apoptosis were increased by homoeopathic drugs. CONCLUSION: These data indicate that apoptosis is one of the mechanisms of tumor reduction of homeopathic drugs. A comparison of potentiated drugs with their mother tincture indicated that the potentiated drugs have biological activity similar to that of their mother tincture in spite of ultradilution.

Dynamized preparations in cell culture.

Although reports on the efficacy of homeopathic medicines in animal models are limited, there are even fewer reports on the in vitro action of these dynamized preparations. We have evaluated the cytotoxic activity of 30C and 200C potencies of ten dynamized medicines against Dalton's Lymphoma Ascites, Ehrlich's Ascites Carcinoma, lung fibroblast (L929) and Chinese Hamster Ovary (CHO) cell lines and compared activity with their mother tinctures during short-term and long-term cell culture. The effect of dynamized medicines to induce apoptosis was also evaluated and we studied how dynamized medicines affected genes expressed during apoptosis. Mother tinctures as well as some dynamized medicines showed significant cytotoxicity to cells during short and long-term incubation. Potentiated alcohol control did not produce any cytotoxicity at concentrations studied. The dynamized medicines were found to inhibit CHO cell colony formation and thymidine uptake in L929 cells and those of Thuja, Hydrastis and Carcinosinum were found to induce apoptosis in DLA cells. Moreover, dynamized Carcinosinum was found to induce the expression of p53 while dynamized Thuja produced characteristic laddering pattern in agarose gel electrophoresis of DNA. These results indicate that dynamized medicines possess cytotoxic as well as apoptosis-inducing properties.