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Cytotoxic effects of ultra-diluted remedies on breast cancer cells Authors: Moshe Frenkel, Bal Mukund Mishra, Subrata Sen, Peiying Yang, Alison Pawlus, Luis Vence, Aimee Leblanc, Lorenzo Cohen, Pratip Banerji, Prasanta Banerji
Affiliations: Integrative Medicine Program-Unit 145, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. [email protected] Pages: 395-403
Abstract: The use of ultra-diluted natural products in the management of disease and treatment of cancer has generated a lot of interest and controversy. We conducted an in vitro study to determine if products prescribed by a clinic in India have any effect on breast cancer cell lines. We studied four ultra-diluted remedies (Carcinosin, Phytolacca, Conium and Thuja) against two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from immortalized normal human mammary epithelial cells (HMLE). The remedies exerted preferential cytotoxic effects against the two breast cancer cell lines, causing cell cycle delay/arrest and apoptosis. These effects were accompanied by altered expression of the cell cycle regulatory proteins, including downregulation of phosphorylated Rb and upregulation of the CDK inhibitor p27, which were likely responsible for the cell cycle delay/arrest as well as induction of the apoptotic cascade that manifested in the activation of caspase 7 and cleavage of PARP in the treated cells. The findings demonstrate biological activity of these natural products when presented at ultra-diluted doses. Further in-depth studies with additional cell lines and animal models are warranted to explore the clinical applicability of these agents.
In summary, our study demonstrates that the ultra-diluted natural product remedies prescribed in the ‘Banerji Protocol’ induce cell cycle delay/arrest with subsequent apoptosis in breast adenocarcinoma cells. Though the degree of the antisurvival effect appeared to correlate with the presence of the wild-type p53 gene, overall susceptibility to the inhibitory effects of the remedies appeared independent of the functional p53 and estrogen-receptor status of the breast carcinoma cells. Finally, the preferentially elevated cytotoxic effects on breast adenocarcinoma cells compared with cells derived from normal mammary epithelium raises the exciting possibility of a window of therapeutic opportunity for preferentially eliminating breast cancer cells with minimal damage to the surrounding normal mammary tissue by using the ultra-diluted remedies investigated in this report. The findings of this study should encourage further preclinical and animal investigation of these remedies as preventive and/or therapeutic treatments for breast cancer.
Ellanzhiyil Surendran Sunila, Ramadasan Kuttan, Korengath Chandran Preethi and Girija Kuttan Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala–680 555, India Abstract
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 ofdynamized 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 shortand 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 expressionof 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.
Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication
Fernando SF Guimarães, Ana PR Abud, Simone M Oliveira, Carolina C Oliveira, Beatriz César, Lucas F Andrade, Lucélia Donatti, Juarez Gabardo, Edvaldo S Trindade, and Dorly F Buchi
Departamento de Biologia Celular, Laboratório de Pesquisa em Células Inflamatórias e Neoplásicas, Universidade Federal do Paraná (UFPR), Curitiba – PR, Brazil Abstract
Background Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180
Conclusion Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells.
Homeopathic medicines for adverse effects of cancer treatments
Sosie Kassab, Mike Cummings, Saul Berkovitz, Robbert van Haselen, Peter Fisher
Royal London Homoeopathic Hospital, London, UK. 2British Medical Acupuncture Society, London, UK. 3INTMEDI, Surrey, UK
Homeopathic medicines are used by many patients with cancer, usually alongside conventional treatment. Cancer treatments can cause adverse effects, and one of the reasons patients use homeopathic medicines is to help with these symptoms. This review looked at whether these medicines could help patients with problems caused by cancer treatments. Eight studies with a total of 664 participants were included in this review. Three studied adverse effects of radiotherapy, three studied adverse effects of chemotherapy and two studied menopausal symptoms associated with breast cancer treatment. Two studies with low risk of bias demonstrated benefit: one with 254 participants demonstrated benefits from calendula ointment in the prevention of radiotherapy-induced dermatitis, and another with 32 participants demonstrated benefits from Traumeel S (a complex homeopathic medicine) over placebo as a mouthwash for chemotherapy-induced stomatitis. These trials need replicating. Two other studies reported positive results, although the risk of bias was unclear, and four further studies reported negative results. The homeopathic medicines used in all eight studies did not seem to cause any serious adverse effects or interact with conventional treatment. No cancer treatments were modified or stopped because of the homeopathic interventions.
Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer
SEN PATHAK1,2, ASHA S. MULTANI1, PRATIP BANERJI3 and PRASANTA BANERJI3
Departments of 1Cancer Biology and 2Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; 3PBH Research Foundation, 10/3/1 Elgin Road, Kolkata 700 020, West Bengal, India Abstract. Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human bloodlymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.
Source : INTERNATIONAL JOURNAL OF ONCOLOGY 23: 975-982, 2003 975 LINK TO FULL ARTICLE
Can homeopathic treatment slow prostate cancer growth?
Samueli Institute, 1700 Diagonal Road, Suite 400, Alexandria, VA 22314, USA.
BACKGROUND: Homeopathy is a complementary medicine widely used around the world. Despite extensive use of homeopathy for cancer and other serious conditions with reported success, clinical and laboratory research has been equivocal, and no rigorous research has been done on cancer. In 1999, the US National Cancer Institute evaluated the effects of homeopathic treatment of cancer from a clinic in India and has released a request for protocols to conduct further research into this treatment. Therefore, the authors conducted a series of carefully controlled laboratory studies evaluating the effects of commonly used homeopathic remedies in cell and animal models of prostate cancer. STUDY DESIGN: One hundred male Copenhagen rats were randomly assigned to either treatment or control groups after inoculation with prostate tumor cells. METHODS: Prostate tumor cells DU-145, LNCaP, and MAT-LyLu were exposed to 5 homeopathic remedies. Male Copenhagen rats were injected with MAT-LyLu cells and exposed to the same homeopathic remedies for 5 weeks. In vitro outcomes included tumor cell viability and apoptosis gene expression. In vivo outcomes included tumor incidence, volume, weight, total mortality, proliferating cell nuclear antigen (PCNA) expression, apoptotic cell death (terminal deoxynucleotidyl transferase mediated d-uridine triphosphate nick end labeling), and gene expression (rAPO-multiprobe). RESULTS: There were no effects on cell viability or gene expression in 3 prostate cell lines with any remedies at any exposure time. There was a 23% reduction in tumor incidence (P < .0001), and for animals with tumors, there was a 38% reduction in tumor volume in homeopathy-treated animals versus controls (P < .02). At time of killing, experimental animals with tumors had a 13% lower average tumor weight (P < .05). Tumors in these treated animals showed a 19% increase in apoptotic cell death (P < .05) and reduced PCNA-positive cells. CONCLUSIONS: The findings indicate that selected homeopathic remedies for the present study have no direct cellular anticancer effects but appear to significantly slow the progression of cancer and reduce cancer incidence and mortality in Copenhagen rats injected with MAT-LyLu prostate cancer cells.
Effect of Homeopathic Medicines on Transplanted Tumors in Mice
ES Sunila, Girija Kuttan, Preethi KC, Ramadasan Kuttan*
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala State, India. 680555. Tel: 91-487- 230- 4190, Fax: 91-487-230-7868,
Abstract 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 γ-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.