Heteroctenus junceus Scorpion Venom Modulates the Concentration of Pro-Inflammatory Cytokines in F3II Tumor Cells.

The ability of Heteroctenus junceus scorpion venom to modulate the concentration of cytokines related to its antitumoral effect is unknown. F3II cells were treated with » IC50, ½ IC50 and the IC50 of H. junceus scorpion venom. Tumor growth kinetics in F3II-bearing mice were evaluated after 24 days of oral administration of venom doses. The effect of tumor lysates on F3II cell viability was evaluated by MTT assay, while cytokines present in each sample were determined by ELISA. In supernatant, H. junceus scorpion venom decreased the concentration of IL-6 (p < 0.001), IFN-γ (p < 0.001), IL-1ß (p < 0.01); meanwhile IL-12 (p < 0.001) and TNF-α (p < 0.001) levels increased significantly, according to the concentration and the time of incubation. Heteroctenus junceus scorpion venom effectively inhibits in vivo tumor progression. In the sera, a significant decrease was observed in TNF-α levels (p < 0.05). In tumor lysates, IL-6 decreased significantly in the groups treated with 12.5 mg/kg (p < 0.001) and 25 mg/kg (p < 0.05). Heteroctenus junceus scorpion venom is capable of modulating other proinflammatory and protumoral cytokines involved in the inflammation associated with cancer.

Agaricus bisporus ß-(1 → 6)-d-glucan induces M1 phenotype on macrophages and increases sensitivity to doxorubicin of triple negative breast cancer cells.

Mushroom ß-d-glucans have demonstrated immunomodulatory activity, which is initiated by their recognition by specific receptors on immune system cells surfaces. Studies indicated that ß-d-glucans may present a synergistic effect with chemotherapy drugs. In this study, a linear ß-(1 â†’ 6)-d-glucan (B16), isolated from A. bisporus and previously characterized (Mw: 8.26 × 104 g/mol), was evaluated about its capacity to modulate THP-1 macrophages towards an M1 phenotype and induce an antitumoral activity. This was evidenced by the production of pro-inflammatory markers upon B16 treatment (30; 100 µg/mL). The breast tumor cells (MDA-MB-231) viability was not affected by treatment with B16, however, their viability markedly decreased upon treatment with the drug doxorubicin. The results showed a synergic effect of B16 and doxorubicin, which reduced the viability of MDA-MB-231 cells by 31%. Furthermore, B16 treatment provided a sustainable M1 state environment and contributed to increase the sensitivity of breast cancer cells to the doxorubicin treatment.

PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy.

Quercetin, a multifunctional therapeutic agent, is used in various types of cancer. However, its therapeutic effect is limited by virtue of poorly aqueous solubility and instability in the physiological medium. To overcome these limitations, we aimed (i) to design quercetin loaded liposomes with unlinked-PEG4000 with regard to not only surface modification but also solubility enhancement, and (ii) to investigate the antineoplastic effects on HeLa cells. PEG4000 increased the quercetin solubility 2.2 fold. PEG4000 modified liposomes displayed small particle size (254 ± 69 nm), low polydispersity index (0.236 ± 0.018), favorable zeta potential (-35.4 ± 0.6 mV), high quercetin encapsulation efficiency (87.6 ± 5.6%), and drug loading (22.2 ± 6.9%). The homogeneity and particle size of stable PEGylated liposomes were proved by transmission electron microscopy. The drug release was reached up to 65.1 ± 3.8% in 6 h. The IC50 value of quercetin loaded PEGylated liposomes was 16.3 µg/mL on HeLa cells, while that of quercetin was 88.3 µg/mL. PEGylated liposomes remarkably hampered the adherence and colony formation ability of cells according to crystal violet staining tests. The convenience of PEGylated liposomes for the parenteral application was stated by the hemolysis assay. The high-throughput screening assays based on AO/PI staining proved the drastic decrease of viable cell count. Moreover, qPCR tests based on gene expression levels revealed that the quercetin loaded PEGylated liposomes treatment could be more effective than free quercetin on the mitochondrial apoptosis of HeLa cells. These promising results allow considering further in vivo studies for efficient cancer treatment with quercetin loaded PEG4000 modified liposomes.

Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin's (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment.

Vertebroplasty shows no antitumoral effect on vertebral metastasis: a case-based study on anatomopathological examinations.

PURPOSE: Percutaneous vertebroplasty (VTP) is a well-known surgical technique used for pain management and vertebral consolidation in the treatment of osteolytic metastases of the spine. While this indication is proven and commonly accepted, an antitumoral effect of polymethylmethacrylate (PMMA) has been proposed but not yet demonstrated. The aim of our study is to evaluate the evidences of antitumoral effect on anatomopathological examination. We present a small series of pathology findings after VTP for spine metastases that support the lack of antitumoral effect of PMMA. METHODS: We have retrospectively analyzed three cases of patients treated for en bloc excision of recurrent spine metastases previously submitted elsewhere to VTP on the same levels. We discuss our results with the literature reporting of an antitumoral effect of VTP. RESULTS: In our series, after anatomopathological examination, a cement-induced tumor necrosis was never found. Conversely, a foreign-body reaction around the cement was found, inside vital tumor. These results are consistent with an immune reaction to a foreign body without evidences of an antitumoral effect of PMMA. CONCLUSION: The antitumoral effect of PMMA should not be taken into account as an indication for VTP in spinal metastases. It is important not to misuse VTP as a therapy aiming at tumor control. Other therapies such as radiotherapy, radiosurgery and open surgery are available for that purpose.

Anti-tumor properties of silver.

The use of silver dates to the period when people used it to mint coins or forge jewels. Towards the end of the 1960s, Resenmberg reported a study on the antitumor activity of cisplatin, and after a few years, cisplatin began to be used all over the world against different types of neoplasias mainly involving testes, ovaries, tumors of the district head-neck. Laryngeal carcinoma cell line HEP2 and tongue carcinoma cell lines PE15 and PE46, were cultured. Cell lines were treated with increasing concentration Ag in order to evaluate the optimal concentration levels that did not significantly affect cell viability. Basing on these data, the concentration adopted for the treatment was 0.007%. Gene expression profile was carried out for 10 genes belong to cell cycle pathways. Significantly up-regulated genes showed ≥ 2-fold change in expression while significantly down-regulated genes showed ≤ 0.5 -fold change in expression. Treatment appears to not significantly affect gene expression in the HEP2 cell line. In fact the only significantly down-regulated gene was CCNE1. All other genes have an expression comparable to that of untreated control. In recent years, the complexes containing gold and silver have been thoroughly studied for their electronic and chemical capabilities and their potential as a valid alternative in the development of new technologies. Further studies on the mechanisms of the biological effect discovered can become fundamental for the development of new high efficiency drugs with minimal minimum effects for the treatment of malignant neoplasia in humans and animals.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom.

BACKGROUND: Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. METHODS: The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. RESULTS: P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. CONCLUSION: These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom

Background Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. Methods The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. Results P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. Conclusion These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom

Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. Methods: The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. Results: P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. Conclusion: These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.(AU)

Podem as bactérias ácido lácticas probióticas apresentarem efeito antitumoral em modelo animal de câncer de cólon? Uma revisão da literatura / Can probiotic acid lactic bacteria submit antitumor effect in animal model of colon cancer? A review of the literature

O Câncer de cólon é um dos tipos mais comuns de câncer no mundo e a segunda principal causa de morte relacionada a esta doença em países desenvolvidos. Até 75% dos casos estão associados com a alimentação, indicando que uma pessoa pode reduzir o seu risco simplesmente através de modificação na dieta. Estudos em animais demonstram que várias cepas de bactérias ácido lácticas protegem contra o câncer de cólon em roedores, embora os dados em humanos sejam limitados e conflitantes. O objetivo deste estudo foi investigar a eficácia das bactérias ácido lácticas no tratamento e redução do câncer de cólon em modelo animal. Foram realizadas buscas sistemáticas em bases de dados eletrônicas alcançando 1079 artigos relacionados, entretanto apenas 6 artigos foram eleitos de acordo com os critérios de elegibilidade para análise. Todos os artigos avaliados apresentaram resultados satisfatórios quanto à inibição do câncer de cólon em ratos e camundongos ao utilizarem cepas predominantemente do gênero Lactobacillus. Este estudo pode responder a hipótese de que as bactérias ácido lácticas apresentam efeito preventivo e antitumoral contra o câncer de cólon.(AU)

Colon cancer is one of the most common types of cancer in the world and the second leading cause of death related to the disease in developed countries. Up to 75% of cases are associated with eating, indicating that a person can reduce their risk simply through dietary modification. Studies in animals show that various strains of lactic acid bacteria protect against colon cancer in rodents although data in humans are limited and conflicting. The aim of this study was to investigate the efficacy of acid lactic bacteria in the treatment and reduction of colon cancer in animal models. Systematic searches were conducted in electronic databases reaching 1079 related articles, only six articles were elected according instead of to the eligibility criteria for analysis. All reviewed articles showed satisfactory results on the inhibition of colon cancer in rats and mice when using predominantly Lactobacillus strains. This study can answer hypothesis that acid lactic bacteria has antitumor effect against colon cancer.(AU)

Efecto antitumoral in vitro del aceite esencial de Piper aduncum L. (matico) y su toxicidad oral en ratones / Piper aduncum L. (matico) essential oil in vitro antitumoral effect and oral toxicity in mice

Introducción: Piper aduncum (matico) es una especie utilizada por sus propiedades medicinales en desórdenes gastrointestinales y genitourinarios. Objetivos: Evaluar el efecto antitumoral del aceite esencial de Piper aduncum (matico) in vitro en siete líneas celulares tumorales humanas y determinar la toxicidad oral en ratones. Diseño: Experimental. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Líneas celulares tumorales humanas H460, DU-145, ME-180, K562, HT-29, MCF 7, M14, K562; fibroblastos normales de ratón 3T3 y ratones albinos machos Balb/C53. Intervenciones: Las líneas celulares fueron expuestas a cuatro concentraciones del aceite esencial de P. aduncum y 5-fluorouracilo (5-FU). Para la toxicidad oral se utilizó ratones albinos machos Balb C/53 de 40 días post destete, a cinco dosis de tratamiento, evaluándose el número de muertes en cada dosis. Principales medidas de los resultados: Porcentaje de inhibición del crecimiento celular (IC50), dosis letal 50 (DL50). Resultados: El aceite esencial mostró IC50 mayor a 250 ug/mL para las líneas celulares M-14 (r = -0,99; p < 0,01), DU-145 (r = 0,99; p < 0,01), ME-180 (r = -0,99; p < 0,01). Para líneas celulares tumorales H460 (r = -0,99; p < 0,01), MCF-7 (r = -0,99; p < 0,01), K562 (r = -0,99; p < 0,01), HT-29 (r = -0,99; p < 0,01), los niveles de IC50 estuvieron entre 20 ug/mL y 250 ug/mL. DL50 > 2 000 mg/kg. Conclusiones: El aceite esencial de P. aduncum no presentó efecto antitumoral in vitro para las siete líneas celulares tumorales humanas y no fue tóxico.

Introduction: Piper aduncum (matìco) is a medicinal plant used for gastrointestinal and genitourinary disorders. Objectives: To determine the in vitro antitumoral effect of Piper aduncum (matico) essential oil on seven human tumoral cell lines and its oral toxicity in mice. Design: Experimental. Setting: Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biologic material: Human tumoral cell lines HT-29, H-460, MCF-7, M-14, ME-180, DU-145, K-562; and 3T3 fibroblasts and male 40 days post weaning Balb C/53 mice. Interventions: The cell lines HT-29, H-460, MCF-7, M-14, ME-180, DU-145, K-562, and 3T3 were exposed to four different concentrations of Piper aduncum essential oil, and to different 5-fluorouracil concentrations used as a positive control. Cell lines growth inhibition (IC50) was determined using linear regression analysis and DL50 by the number of deaths with each dose. Main outcome measures: Antitumor effect. Results: Piper aduncum essential oil showed cytotoxic activity at IC50 levels > 250 ug/mL on cell lines M-14 (r = -0.99; p < 0.01), DU-145 (r = -0.99; p < 0.01), ME-180 (r = -0.99; p < 0.01). IC50 was between 20 ug/mL and 250 ug/mL on cell lines H-460 (r = -0.99; p < 0.01), MCF-7, (r = -0.99; p < 0.01), K562 (r = -0.99; p < 0.01), HT-29 (r = -0.99; p < 0.01). DL50 was > 2 000 mg/kg. Conclusions: P. aduncum essential oil did not show antitumoral effect on seven human tumoral cell lines and it was non toxic.

Crotalus durissus terrificus venom as a source of antitumoral agents

The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV) and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumoral effect on benign (pituitary adenoma) and malignant (glioblastoma multiforme) tumors with IC50 values of 0.96 ± 0.11 µg/mL and 2.15 ± 0.2 µg/mL, respectively. This antitumoral effect is cell-cycle-specific and dependent on extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumoral effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumoral dose established in vitro was not found to be toxic to the analyzed animals. These results indicate the biotechnological potential of CV as a source of pharmaceutical templates for cancer therapy.

Antitumoral effects of annonaceous acetogenins / 中国药理学通报

A large number of natural acetogenins have been isolated from se veral genera of the plant family Annonaceae. Many of these compounds have very p otent and diverse biological effects such as cytotoxic, antitumour, anti-malari al, pesticidal and anti-feedant activities. This paper reviews research finding s about the effects of annonaceous acetogenins on antitumor, MDR, mechanism of ac tion, structural-activity relationships etc.