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1.
Homeopathy ; 112(3): 160-169, 2023 08.
Article in English | MEDLINE | ID: mdl-36442592

ABSTRACT

BACKGROUND: Arsenic trioxide (As2O3) has been in therapeutic use since the 18th century for various types of cancers including skin and breast; however, it gained popularity following FDA approval for its use against acute promyelocytic leukemia. This present work was designed to evaluate the anti-cancer potential of a homeopathic potency of arsenic trioxide (Arsenicum album 6C) in hormone-dependent breast cancer. METHODS: Breast cancer cells (MCF7) were treated with Arsenicum album (Ars 6C) to evaluate its anti-proliferative and apoptotic potential. We examined the effect of Ars 6C on the cell cycle, wound healing, reactive oxygen species (ROS) generation, and modulation of expression of key genes which are aberrant in cancer. RESULTS: Treating breast cancer cells with Ars 6C halted the cell cycle at the sub-G0 and G2/M phases, which could be attributed to DNA damage induced by the generation of ROS. Apoptotic induction was associated with upregulation of Bax expression, with concurrent downregulation of the Bcl-2 gene. Ars 6C was also seen to reverse epithelial to mesenchymal transition and reduce the migration of breast cancer cells. CONCLUSION: The findings suggest that Ars has significant anti-proliferative and apoptotic potential against breast cancer cells. Further studies are required to elucidate the mechanism by which Ars exerts its effect in the in vivo setting.


Subject(s)
Arsenicals , Breast Neoplasms , Homeopathy , Humans , Female , Arsenic Trioxide/pharmacology , Epithelial-Mesenchymal Transition , Arsenicals/pharmacology , Arsenicals/therapeutic use , Oxides/therapeutic use , Breast Neoplasms/drug therapy , Reactive Oxygen Species/pharmacology , Apoptosis , Cell Cycle Checkpoints , Hormones/pharmacology , MCF-7 Cells , Cell Line, Tumor
2.
J Toxicol Environ Health A ; 84(18): 761-768, 2021 09 17.
Article in English | MEDLINE | ID: mdl-34180377

ABSTRACT

Dipyrone or metamizole is one of the most frequently used analgesic worldwide. Despite its widespread use, this drug may exert genotoxic and cytotoxic effects on lymphocytes. Therefore, studies with therapeutic agents that may provide protection against these effects are important. The homeopathic compound Canova® (CA) appears to be a beneficial candidate for preventing DNA damage and cellular lethality, since this compound acts as an immunomodulator associated with cytoprotective actions. Hence, the aim of the present investigation was to determine the potential cytoprotective effects of CA using cell line VERO as a model. VERO cells were incubated with sodium dipyrone and subsequently subject to the comet, apoptosis and immunocytochemistry assays. Data demonstrated that sodium dipyrone induced an increase in DNA damage index (DI) employing the comet assay. However, when VERO cells were co-treated with CA at the three concentrations studied, a significant reduction in DI was observed, indicating an antigenotoxic effect attributed to CA. Further dipyrone induced an elevation in %apoptosis at 24 and 48 hr. However, when dipyrone was co-incubated with CA, a significant reduction in %apoptosis was noted at the three concentrations of CA employed. Results from immunocytochemical analysis showed a rise in the expression of caspase 8 and cytochrome C when cells were exposed to dipyrone. In contrast, co-treatment of dipyrone and CA significantly reduced the effect of dipyrone. Therefore, evidence indicated that CA acted as an anticytotoxic and antigenotoxic agent counteracting damage induced by dipyrone.


Subject(s)
Crotalid Venoms/pharmacology , Cryoprotective Agents/pharmacology , Dipyrone/adverse effects , Materia Medica/pharmacology , Plant Extracts/pharmacology , Animals , Apoptosis , Chlorocebus aethiops , Comet Assay , Immunohistochemistry , Vero Cells
3.
Altern Ther Health Med ; 27(6): 40-50, 2021 Nov.
Article in English | MEDLINE | ID: mdl-32619203

ABSTRACT

CONTEXT: Cancer occurs as a consequence of the dysregulation of genes during cell division, resulting in an increased proliferation rate and loss of vital checkpoints in cells. Photodynamic therapy (PDT) makes use of photosensitizers, oxygen, and light at visible wavelengths to stimulate formation of reactive oxygen species (ROS) and trigger apoptosis of cancer cells. Homeopathic remedies commonly affect genes, including tumor necrosis factor alpha (TNF-α) and Bcl2, thereby stimulating cancer-cell death. OBJECTIVE: The study intended to examine and summarize the latest findings in preclinical, in vitro, and in vivo studies on the mechanisms of homeopathy and PDT in cancer therapy. DESIGN: The research team conducted a literature review using extensive databases made available by the University of Johannesburg Library. The databases used, included, Science Direct, Ebsco Host and Pubmed. SETTING: This study took place at the Laser Research Centre, University of Johannesburg. RESULTS: Studies demonstrated an ability for both homeopathic remedies and photodynamic therapy to induce apoptosis in cancer cells by interfering with mitochondrial pathways leading to a release of cytochrome-c, the production of reactive oxygen species and by interfering with cancer cell genes by upregulating p53 and Bax and down-regulating TNF-α. CONCLUSIONS: Both homeopathy and PDT demonstrate antineoplastic effects; however; more research needs to be conducted before any conclusions can be made.


Subject(s)
Homeopathy , Materia Medica , Neoplasms , Photochemotherapy , Apoptosis , Cell Line, Tumor , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/pharmacology
4.
Homeopathy ; 109(4): 198-206, 2020 11.
Article in English | MEDLINE | ID: mdl-32610349

ABSTRACT

BACKGROUND: Breast cancer is the second leading cause of cancer-related deaths in women. Conventional treatment such as chemotherapy, hormonal therapy and radiotherapy has decreased the mortality rate among cancer patients but has also revealed long-term side effects. Drug resistance and toxicity to normal cells compound the problems associated with the use of modern medicines. Hence, complementary or alternative treatment options are being explored. The current study, using different homeopathic potencies of Hydrastis canadensis, was conducted to distinguish between any effects they might have on hormone-dependent and independent breast cancer. MATERIALS AND METHODS: The cytotoxic effect of homeopathic medicine Hydrastis on hormone-dependent (MCF 7) and hormone-independent (MDA-MB-468) breast cancer cells was assessed using viability and colony-forming assays after 48 or 72 hours of treatment. Flow cytometry-based Annexin V-PI (propidium iodide), caspase 3 and cell cycle analysis was performed following treatment of cells with mother tincture or various potencies of Hydrastis (1C, 2C, 30C, 200C). RESULTS: Different potencies of Hydrastis displayed selective cytotoxic effects against MCF 7 cells, but only marginal effects against MDA-MB-468. The maximum cytotoxicity was established in the case of 1C following 72 hours of treatment. Treatment of breast cancer cells revealed an increase in the G0/G1 cell population, along with an increase in the caspase 3 levels and induction of apoptosis. CONCLUSION: Hydrastis may have a selective cytotoxic effect against hormone-dependent breast cancer MCF 7 cells, leading to cell cycle arrest in the G0/G1 phase, which could be the plausible reason for the induction of apoptosis. The results need to be validated in vivo.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Homeopathy/methods , Hydrastis , Plant Extracts/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cytotoxins/pharmacology , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , MCF-7 Cells
5.
Homeopathy ; 107(1): 32-39, 2018 02.
Article in English | MEDLINE | ID: mdl-29528476

ABSTRACT

BACKGROUND: Gene expression analysis of cells treated with extreme dilutions or micro amounts of drugs has been used to provide useful suggestions about biological responses. However, most of the previous studies were performed on medicines being prepared from a variety of herbal and metal sources. This study investigated the effects of ultramolecular dilution of the taxane anti-cancer drugs, which are not commonly used in homeopathic medicines, on mRNA expression profiles of five key genes (p53, p21, COX-2, TUBB2A and TUBB3) in the breast cancer cell line MCF-7. METHOD: MCF-7 cells were exposed to paclitaxel (Taxol) or docetaxel (Taxotere) preparations (6X, 5C and 15C dilutions prepared from pharmacological concentration of 25 nmol/L) for 72 hours. The cell culture groups were evaluated with the trypan blue dye exclusion method for the proliferation/cytotoxicity rates, immuno-staining ß-tubulin for microtubule organization, and reverse transcription polymerase chain reaction for gene expression levels.Fold-change in gene expression was determined by the ΔΔCt method. RESULTS: The administration of diluted preparations had little or no cytotoxic effect on MCF-7 cells, but altered the expression of genes analyzed with a complex effect. According to the ΔΔCt method with a five-fold expression difference (p < 0.05) as a cut-off level, ultra-high dilutions of paclitaxel and docetaxel showed differential effects on the studied genes with a concentration-independent activity. Furthermore, the dilutions disrupted the microtubule structure of MCF-7 cells, suggesting that they retain their biological activity. CONCLUSION: Despite some limitations, our findings demonstrate that gene expression alterations also occur with ultra-high dilutions of taxane drugs.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Line, Tumor/drug effects , Gene Expression/drug effects , Homeopathy , Apoptosis/drug effects , Cell Proliferation/drug effects , Female , Humans , MCF-7 Cells
6.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4019-4026, 2018 Oct.
Article in Zh | MEDLINE | ID: mdl-30486525

ABSTRACT

Ferroptosis is a new form of regulated cell death which is different from apoptosis, necrosis and autophagy, and results from iron-dependent lipidperoxide accumulation. Now, it is found that ferroptosis is involved in multiple physiological and pathological processes, such as cancer, arteriosclerosis, neurodegenerative diseases, diabetes, antiviral immune response, acute renal failure, hepatic and heart ischemia/reperfusion injury. On the one hand, it could be found the appropriate drugs to promote ferroptosis to clear cancer cells and virus infected cells, etc. On the other hand, we could inhibit ferroptosis to protect healthy cells. China has a wealth of traditional Chinese medicine resources. Chinese medicine contains a variety of active ingredients that regulate ferroptosis. Here, this paper reported the research of ferroptosis pathway, targets of its inducers and inhibitors that have been discovered, and the regulatory effects of the discovered Chinese herbs and its active ingredients on ferroptosis to help clinical and scientific research.


Subject(s)
Apoptosis , Drugs, Chinese Herbal/pharmacology , Iron , Materia Medica/pharmacology , China , Humans
7.
Zhongguo Zhong Yao Za Zhi ; 43(10): 2134-2139, 2018 May.
Article in Zh | MEDLINE | ID: mdl-29933683

ABSTRACT

The present study was designed to investigate the effect of cultivated Cordyceps sinensis (CCS) on leukemia-derived K562 cells, and further explore the underlying mechanisms. After routine culture of K562 cells, MTT assay was used to detect the effect of CCS on survivel of human leukemia cell lines K562;DAPI staining was used to observe the morphological changes of the nucleus and AO/EB staining was used to observe cell apoptosis. JC-1 staining was employed to detect the changes in mitochondrial membrane potential. Flow cytometry (FCM) was used to detect cell cycle distribution, and Western blot analysis was used to detect the expression levels of Bax, Bcl-2, caspase 3, caspase 8, cyclin D1, CDK2, and CDK4 in K562 cells. The results showed that CCS (0.345-5.524 g·L⁻¹) substantially suppressed proliferation of K562 cells and induced G1/S phase arrest in a dose-dependent manner. DAPI and AO/EB staining indicated that cell apoptosis was significantly induced by CCS treatment, accompanied by decreased mitochondrial membrane potential demonstrated by JC-1 staining. Western blot results showed that CCS significantly increased the expression of Bax and, meanwhile, decreased the expression levels of Bcl-2, cyclin D1, CDK2, CDK4, caspase 3 and caspase 8. Collectively, our data demonstrated that CCS dose-dependently suppressed cell proliferation and induced cell apoptosis in K562 cells, and the mechanism might be associated with inducing cell cycle arrest, regulating Bcl-2/Bax ratio and activating the mitochondrial apoptosis pathway.


Subject(s)
Apoptosis , Cell Proliferation , Cordyceps/chemistry , Materia Medica/pharmacology , Apoptosis Regulatory Proteins/metabolism , Humans , K562 Cells
8.
Microb Pathog ; 110: 107-116, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28645772

ABSTRACT

Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease.


Subject(s)
Apoptosis/drug effects , Chagas Disease/drug therapy , Hepatocytes/drug effects , Lycopodium/chemistry , Plant Extracts/therapeutic use , Spleen/drug effects , Trypanosoma cruzi/pathogenicity , Animals , Body Temperature , Chagas Disease/physiopathology , Conium/chemistry , Cytokines/metabolism , DNA Fragmentation , Disease Models, Animal , Drinking , Hepatocytes/parasitology , Hepatocytes/pathology , Interleukin-4/metabolism , Interleukin-6/metabolism , Male , Mice , Morbidity , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Spleen/parasitology , Spleen/pathology , Survival Rate , Th1 Cells/immunology , Th2 Cells/immunology , Trypanosoma cruzi/immunology , Tumor Necrosis Factor-alpha/metabolism , Weight Gain
9.
Homeopathy ; 106(1): 32-36, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28325222

ABSTRACT

BACKGROUND: Several recent studies reported the capability of high diluted homeopathic medicines to modulate gene expression in cell cultures. In line with these studies, we examined whether ultra-high dilutions (30C and 200C) of sodium butyrate (SB) can affect the expression levels of genes involved in acquisition of a senescence-associated secretory phenotype (SASP) in human embryonic kidney (HEK) 293 cells. METHODS: Cell viability was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of TNF-α, interleukin (IL)-2, IL-4, IL-6 and IL-10 genes were determined by real-time PCR assay. RESULTS: Exposure to both 30C and 200C during 48 h led to a significant decrease of the level of expression of TNF-α gene, while expression of IL-2 gene was increased when exposed to 30C, and expression of IL-10 gene was decreased when exposed to 200C. No changes in expression levels of all genes studied were observed in cells treated with both 30C and 200C remedies of SB during the 24 h. CONCLUSION: Observed changes in gene expression levels after exposure to 30C and 200C remedies of SB during 48 h suggest that extremely low concentrations of this agent can modulate the transcriptome of HEK 293 cells. These results are in line with findings from other studies confirming the ability of homeopathic remedies to modulate gene expression in cell cultures.


Subject(s)
Antineoplastic Agents/pharmacology , Butyric Acid/pharmacology , Homeopathy , Apoptosis/drug effects , Gene Expression Regulation , HEK293 Cells/drug effects , HEK293 Cells/metabolism , Humans , Interleukin-10/metabolism , Interleukin-2/metabolism , Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/metabolism
10.
Lab Invest ; 96(12): 1279-1300, 2016 12.
Article in English | MEDLINE | ID: mdl-27775689

ABSTRACT

Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.


Subject(s)
Antioxidants/therapeutic use , Disease Models, Animal , Lung/drug effects , Materia Medica/therapeutic use , Oligochaeta/chemistry , Pulmonary Fibrosis/prevention & control , Silicosis/drug therapy , Tissue Extracts/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/administration & dosage , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line , Cells, Cultured , Epithelial-Mesenchymal Transition/drug effects , Injections, Intraperitoneal , Lung/metabolism , Lung/pathology , Lung/physiopathology , Male , Materia Medica/administration & dosage , Materia Medica/pharmacology , Mice, Inbred C57BL , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/immunology , RNA Interference , Random Allocation , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Silicosis/metabolism , Silicosis/pathology , Silicosis/physiopathology , Specific Pathogen-Free Organisms , Tissue Extracts/administration & dosage , Tissue Extracts/pharmacology
11.
J Neurooncol ; 128(1): 9-19, 2016 05.
Article in English | MEDLINE | ID: mdl-26900077

ABSTRACT

The most aggressive type of brain tumor is glioblastoma multiforme, which to date remains incurable. Thuja occidentalis is used in homeopathy for the treatment of cancer, however, its mechanism of action remains unknown. We set out to study the effects of thujone fractions of Thuja on glioblastoma using in vitro and in vivo models. We found that the α/ ß-thujone fraction decrease the cell viability and exhibit a potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro. In vivo assays showed that α /ß-thujone promotes the regression of neoplasia and inhibits the angiogenic markers VEGF, Ang-4 and CD31 into the tumor.


Subject(s)
Antineoplastic Agents/pharmacology , Glioblastoma/drug therapy , Monoterpenes/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Thuja , Angiogenesis Inhibitors/pharmacology , Animals , Apoptosis/drug effects , Bicyclic Monoterpenes , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Glioblastoma/blood supply , Glioblastoma/pathology , Glioblastoma/physiopathology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/physiology , Humans , Male , Neoplasm Transplantation , Rats, Sprague-Dawley
12.
Cell Mol Biol (Noisy-le-grand) ; 62(11): 76-80, 2016 Sep 30.
Article in English | MEDLINE | ID: mdl-27755956

ABSTRACT

The current study is aimed at investigation of the opium effects on the apoptosis of different cell lines in culture medium and compares such effects with one another. The study is carried out on over 8 cell lines (AA8, AGS, Hela, HepG2, MCF7, N2a, PC12, WEHI). A 2.86 x 10-4 g/ml opium concentration was prepared and added to the culture medium of the cell lines for 48 hours. Cytotoxicity was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic effect of opium on the cell lines was analyzed by Annexin-PI test. Opium with concentration of 2.86 x 10-4 g/ml in 48 hours significantly induces apoptosis in certain cell lines (i.e. AA8, N2a, WEHI), apoptosis and necrosis in some others (i.e. Hela, HepG2, MCF7, and PC12), and also solely necrosis in the AGS cell line. One could infer that the usage of opium with different levels in different tissues leads to certain disorders in some tissues and may have therapeutic effects under distinctive conditions (i.e. unchecked growth of cells) as confirmed by the results.


Subject(s)
Apoptosis/drug effects , Opium/toxicity , Animals , Cell Line , HeLa Cells , Hep G2 Cells , Humans , MCF-7 Cells , PC12 Cells , Rats
13.
Homeopathy ; 105(3): 250-256, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27473546

ABSTRACT

BACKGROUND: As a therapeutic system, homeopathy is supported by: i) similitude and experimentation in healthy individuals, ii) potentization. A challenge for researchers consists in looking for signals in water (or vehicle) to explain the storage of information in extremely high dilutions and the transfer of such information to the living systems. Anuran amphibian metamorphosis is controlled by thyroid hormones (TH), including the resorption of the tadpole tail. Apoptosis is a genetically regulated form of cell death that can be triggered by various extracellular and intracellular stimuli resulting in coordinated activation of a family of cysteine proteases called caspases. METHODS: This study was blind and randomized. It performed in three stages: I) the identification of the most effective T3 homeopathic dilution to induce apoptotic reactions in Rana (Lithobates) catesbeianus tadpole tail explants stimulated by T3 in substantial, II) study of different controls and III) detection in explants under the action of the most effective dilution of T3, as established in Stage I. RESULTS: There was no statistically significant difference between tail macroscopic dimensions between the groups. T3 10cH decreased the expression of caspase 3/7 mRNA, in explants treated with T3 20 nM. CONCLUSION: The present experiment is in agreement with the hypothesis that T3, at a 10cH homeopathic dilution, changes the metamorphosis molecular network.


Subject(s)
Apoptosis/drug effects , Larva/drug effects , Materia Medica/chemistry , Metamorphosis, Biological/drug effects , Triiodothyronine/pharmacology , Animals , Homeopathy , Organ Culture Techniques , Rana catesbeiana , Tail/drug effects
14.
Homeopathy ; 105(3): 265-269, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27473548

ABSTRACT

BACKGROUND: CANOVA(®) (CA) is a homeopathic immunomodulator. It contains several homeopathic medicines prepares according to the Brazilian Pharmacopoeia. CA is indicated in clinical conditions in which the immune system is impaired and against tumors. N-methyl-N-nitrosourea (NMU) is an N-nitroso compound, with genotoxic/mutagenic properties. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects. METHOD: This study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used. The genotoxicity/antigenotoxicity of CA was evaluated by the comet assay, anticytotoxicity was assessed by quantification of apoptosis and necrosis using acridine orange/ethidium bromide. RESULTS: CA significantly reduced DNA damage induced by NMU and reduced significantly the frequency of NMU-induced apoptosis after 24 h of treatment. CONCLUSION: CA has an important cytoprotective effect significantly reducing the DNA damage and apoptosis induced by the carcinogen NMU.


Subject(s)
Crotalid Venoms/pharmacology , Cytoprotection , DNA Damage/drug effects , Homeopathy , Lymphocytes/drug effects , Plant Extracts/pharmacology , Adult , Apoptosis , Cells, Cultured , Female , Humans , Male , Methylnitrosourea/adverse effects , Mutagenicity Tests
15.
Homeopathy ; 104(1): 36-47, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25576270

ABSTRACT

In the present study, we investigated the anti-cancer effect of various potencies of Ruta graveolens (Ruta) on COLO-205 cell line, as evidenced by cytotoxicity, migration, clonogenecity, morphological and biochemical changes and modification in the levels of genes associated with apoptosis and cell cycle. On treatment of COLO-205 cells maximal effects were seen with mother tincture (MT) and 30C potencies, wherein decrease in cell viability along with reduced clonogenecity and migration capabilities were noted. In addition morphological and biochemical alterations such as nuclear changes (fragmented nuclei with condensed chromatin) and DNA ladder-like pattern (increased amount of fragmented DNA) in COLO-205 cells indicating apoptotic related cell death were seen. The expression of apoptosis and cell-cycle related regulatory genes assessed by reverse transcriptase-PCR revealed an up-regulation of caspase 9, caspase-3, Bax, p21 and p27 expression and down-regulation of Bcl-2 expression in treated cells. The mode of cell death was suggestive of intrinsic apoptotic pathway along with cell cycle arrest at the G2/M of the cell cycle. Our findings indicate that phytochemicals present in Ruta showed potential for natural therapeutic product development for colon carcinoma.


Subject(s)
Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Colonic Neoplasms/drug therapy , DNA Fragmentation/drug effects , Ruta , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Colonic Neoplasms/pathology , Flow Cytometry , Humans
16.
ScientificWorldJournal ; 2014: 452892, 2014.
Article in English | MEDLINE | ID: mdl-24672319

ABSTRACT

The purpose of this current study was to justify the incorporation of complementary and alternate medicine (CAM) in current cancer treatments. The major drawback of anticancer drugs is their nonselective killing, which ultimately leads to attrition of normal cells. Keeping this as the foundation of our study, we made an effort to compare the cytotoxicity associated with a known chemotherapeutic drug 5-Fluorouracil (5-FU), with certain CAM therapies previously reported to have anticancer activity. The parameters chosen for the study were based on antiproliferative and cytotoxic effects on normal, kidney epithelial cells (NRK-52E). The MTT assay, colony formation assay, DNA fragmentation, and differential staining using AO/EB, following treatment with either 5-FU or CAM therapies, were performed. The CAM therapies under study were various extracts of wheatgrass, roots of Achyranthes aspera (AA), mushroom extracts (Pleurotus ostreatus, Macrolepiota procera, and Auricularia polytricha), and a homeopathic drug, Ruta graveolens (Ruta). The results showed that treatment of normal cells with the CAM therapies led to minimum cell damage in comparison to 5-FU. This evidence-based study will lead to greater acceptance of alternative therapies against cancer.


Subject(s)
Cell Survival/drug effects , Complementary Therapies , Apoptosis , Cell Line , Humans , In Vitro Techniques , Kidney/cytology , Kidney/drug effects
17.
Zhong Yao Cai ; 37(2): 199-201, 2014 Feb.
Article in Zh | MEDLINE | ID: mdl-25095334

ABSTRACT

OBJECTIVE: To study the therapeutic effects of Bufonis Venenum on L7212 leukemia and the potential mechanism. METHODS: L7212 leukemia model mice were randomly divided into four groups: model group, low and high dose Bufonis Venenum groups and chemotherapy group. Normal mice were treated as control group. Mice were injected intraperitoneally for 10 days continually. The body weight, survival time, peripheral blood leukocyte, hepatic and splenic indexes, bone marrow leukocyte and T lymphocyte were observed and determined. RESULTS: Body weight of L7212 leukemia model group mice were decreased significantly. Compared with other groups, high dose Bufonis Venenum group's weight loss was the least. Bufonis Venenum groups survived longer than L7212 model group. Compared with model group, high dose Bufonis Venenum group's liver index was higher (P < 0.05). After inoculation for 1 day, leukocyte count as well as percentage of leukemic cells within five groups had no significant difference (P > 0.05). Compared with the model group, after inoculation for 10 days, leukocyte count in Bufonis Venenum groups and the chemotherapy group were significantly reduced (P < 0.05). Percentage of leukemia cells in blood and bone marrow in high dose Bufonis Venenum group was significantly decreased (P < 0.05). Compared with model group, CD3+ and CD4+ in Bufonis Venenum groups and the chemotherapy group were increased, CD8+ was decreased, but had no significant difference (P > 0.05). CONCLUSION: Bufonis Venenum has therapeutic effects on the L7212 leukemia by inducing apoptosis and improving immune system.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Bufanolides/pharmacology , Bufonidae , Leukemia, Experimental/drug therapy , Materia Medica/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Body Weight , Bufanolides/administration & dosage , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Leukemia, Experimental/immunology , Leukocyte Count , Male , Materia Medica/administration & dosage , Mice , Mice, Inbred Strains , Neoplasm Transplantation , Random Allocation , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology
18.
J Ethnopharmacol ; 333: 118406, 2024 Oct 28.
Article in English | MEDLINE | ID: mdl-38838923

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms. AIM OF THE STUDY: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug. MATERIALS AND METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels. RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum. CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.


Subject(s)
Caenorhabditis elegans , Animals , Mice , Caenorhabditis elegans/drug effects , Male , Apoptosis/drug effects , Female , Reproduction/drug effects , Lung/drug effects , Lung/pathology , Lung/metabolism , Materia Medica/toxicity , Medicine, Chinese Traditional , Metabolomics , Toxicity Tests
19.
Mol Cell Biochem ; 382(1-2): 173-83, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23807740

ABSTRACT

Gonolobus condurango plant extract is used as an anticancer drug in some traditional systems of medicine including homeopathy, but it apparently lacks any scientific validation. Further, no detailed study is available to suggest whether condurango-glycoside-A (CGA), a major ingredient of condurango serves as a potent anticancer compound. Therefore, we investigated apoptosis-inducing ability of CGA against cervix carcinoma cells (HeLa). ß-galactosidase-activity and DNA damage were critically studied at different time points; while induced DNA-damage was observed at 9-12th hours, senescence of cells appeared at a later stage (18th hour after CGA treatment), implicating thereby a possible role of DNA damage in inducing pre-mature cell senescence. Concurrently, the number of cells undergoing apoptosis increased along with increase in reactive oxygen species (ROS) generation. Expression of p53 was also up-regulated, indicating that apoptosis could have been mediated through p53 pathway. DCHFDA (4',6-Diamidino-2-phenylindole dihydrochloride) assay, acridine orange/ethidium bromide staining and annexin V/PI assay results collectively confirmed that apoptosis was induced by increased ROS generation. Reduction in proliferation of cells was further evidenced by the cell cycle arrest at G0/G1 stage. Expression profiles of certain relevant genes and proteins like p53, Akt, Bcl-2, Bax, cytochrome c and caspase 3 also provided evidence of ROS mediated p53 up-regulation and further boost in Bax expression and followed by cytochrome c release and activation of caspase 3. Overall results suggest that CGA initiates ROS generation, promoting up-regulation of p53 expression, thus resulting in apoptosis and pre-mature senescence associated with DNA damage.


Subject(s)
Apoptosis/drug effects , Cellular Senescence/drug effects , DNA Damage , Marsdenia/chemistry , Pregnanes/pharmacology , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism , Apoptosis/genetics , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/genetics , Cell Movement/drug effects , Cell Movement/genetics , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell Survival/genetics , Cellular Senescence/genetics , G1 Phase/drug effects , G1 Phase/genetics , Gene Expression Regulation, Neoplastic/drug effects , HeLa Cells , Humans , Mass Spectrometry , Pregnanes/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Resting Phase, Cell Cycle/drug effects , Resting Phase, Cell Cycle/genetics , Signal Transduction/drug effects , Signal Transduction/genetics
20.
BMC Complement Altern Med ; 13: 230, 2013 Sep 21.
Article in English | MEDLINE | ID: mdl-24053127

ABSTRACT

BACKGROUND: Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. However, the molecular mechanisms underneath the anti-cancer effect, if any, of these medicines have still remained unexplored. To this end we attempted to evaluate the efficacy of calcarea carbonica, a homeopathic medicine, as an anti-cancer agent and to delineate the detail molecular mechanism(s) underlying calcerea carbonica-induced tumor regression. METHODS: To investigate and delineate the underlying mechanisms of calcarea carbonica-induced tumor regression, Trypan blue dye-exclusion test, flow cytometric, Western blot and reverse transcriptase-PCR techniques were employed. Further, siRNA transfections and inhibitor studies were used to validate the involvement of p53 pathway in calcarea carbonica-induced apoptosis in cancer cells. RESULTS: Interestingly, although calcarea carbonica administration to Ehrlich's ascites carcinoma (EAC)- and Sarcoma-180 (S-180)-bearing Swiss albino mice resulted in 30-35% tumor cell apoptosis, it failed to induce any significant cell death in ex vivo conditions. These results prompted us to examine whether calcarea carbonica employs the immuno-modulatory circuit in asserting its anti-tumor effects. Calcarea carbonica prevented tumor-induced loss of effector T cell repertoire, reversed type-2 cytokine bias and attenuated tumor-induced inhibition of T cell proliferation in tumor-bearing host. To confirm the role of immune system in calcarea carbonica-induced cancer cell death, a battery of cancer cells were co-cultured with calcarea carbonica-primed T cells. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells by calcarea carbonica i.e., (1) activation of the immune system of the host; and (2) induction of cancer cell apoptosis via immuno-modulatory circuit in p53-dependent manner by down-regulating Bcl-2:Bax ratio. Bax up-regulation resulted in mitochondrial transmembrane potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNA-interference inhibited calcarea carbonica-induced apoptosis thereby confirming the contribution of p53. CONCLUSION: These observations delineate the significance of immuno-modulatory circuit during calcarea carbonica-mediated tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea carbonica into immunotherapeutic strategies for effective tumor regression.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Calcium Carbonate/pharmacology , Tumor Suppressor Protein p53/metabolism , Animals , Antineoplastic Agents/chemistry , Breast Neoplasms , Calcium Carbonate/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation/drug effects , Female , Humans , Mice , Mitochondria/drug effects , T-Lymphocytes, Helper-Inducer/drug effects , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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