RESUMO
Cardiac glycosides (CGs) are natural compounds widely used in the treatment of several cardiac conditions and more recently have been recognized as potential antitumor compounds. They are known to be ligands for Na/K-ATPase, which is a promising drug target in cancer. More recently, in addition to their antitumor effects, it has been suggested that CGs activate tumor-specific immune responses. This review summarizes the anticancer aspects of CGs as new strategies for immunotherapy and drug repositioning (new horizons for old players), and the possible new targets for CGs in cancer cells.
Assuntos
Antineoplásicos/uso terapêutico , Glicosídeos Cardíacos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Animais , Humanos , ATPase Trocadora de Sódio-Potássio/imunologiaRESUMO
BACKGROUND: Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. METHODS: The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. RESULTS: The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 µg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. CONCLUSION: T. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Glicosídeos Cardíacos/uso terapêutico , Flavonas/uso terapêutico , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Thevetia/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Glicosídeos Cardíacos/análise , Glicosídeos Cardíacos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Fragmentação do DNA , Feminino , Flavonas/análise , Flavonas/farmacologia , Frutas , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , México , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Células VeroRESUMO
Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour cells frequently express different pump isoforms. Thus, Na/K-ATPase is a powerful target for lung cancer treatment. Drugs targeting Na/K-ATPase may induce apoptosis and autophagy in transformed cells. We argue that Na/K-ATPase has a role as a potential target in chemotherapy in lung cancer treatment. We discuss the effects of Na/K-ATPase ligands and molecular pathways inducing deleterious effects on lung cancer cells, especially those leading to apoptosis and autophagy.
Assuntos
Antineoplásicos/farmacologia , Glicosídeos Cardíacos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glicosídeos Cardíacos/uso terapêutico , Humanos , Neoplasias Pulmonares/enzimologia , Terapia de Alvo MolecularRESUMO
For more than 200 years, cardiotonic glycosides have been used for the treatment of congestive heart failure. Ouabain is a well-known arrow poison obtained from different Acokanthera or Strophanthus species. Much information has now accumulated that this plant toxin and its congeners are mammalian steroid hormones involved in the pathophysiology of cardiovascular diseases. There is an interesting fact that 50% patients with essential hypertension have elevated levels of endogenous ouabain. A better knowledge of the interactions of these compounds with the hormones of salt and water metabolism might help to improve the diagnosis and therapy of hypertension.
Assuntos
Glicosídeos Cardíacos/uso terapêutico , Hormônios/fisiologia , Ouabaína/farmacologia , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Glicosídeos Cardíacos/farmacologia , Hormônios/farmacologia , Hormônios/uso terapêutico , Humanos , Ouabaína/uso terapêutico , Esteroides/farmacologia , Esteroides/fisiologia , StrophanthusRESUMO
O fator mais importante na intoxicaçäo digitálica é o seu reconhecimento. A intoxicaçäo continua sendo comum e de difícil confirmaçao. Isto se deve às semelhanças existentes entre arritmias, sintomas geraos pela intoxicaçäo digitálica e doença cardíaca de base. Além disso, os níveis plasmáticos terapêuticos da digoxina apresentam alto grau de variabilidade e muitas vezes sobrepöm-se aos da toxicidade, näo servindo, portanto, como parâmetro diagnóstico, especialmente na emergência. A intoxicaçäo pela digital, complicaçäo potencialmente fatal, inclui também os pacientes que ingerem doses maciças na medicaçäo intencional ou acidentalmente. A terapia convencional continua sendo a reposiçäo de potássio sempre que necessário, objetivando manter nível plasmático igual ou superior a 4 mEq/l, o controle dos níveis do magnésio e cálcio, correçäo do balanço hídrico e ácido-básico, bem como a adminstraçäo de antiarrítmicos apropriados ou a instalaçäo de marcapasso temporário. A aquisiçäo terapêutica mais recente é o uso de anticorpo antidigoxina (Fab), que apesar do seu alto custo, quando bem indicado, constitui tratamento efetivo. O objetivo deste artigo é rever o mecanismo de açäo da digital, realçar as manifestaçöes cardíacas e extracardíacas da intoxicaçäo, rever a importância da determinaçäo dos níveis séricos da digital e as alternativas terapêuticas.
Assuntos
Humanos , Fibrilação Atrial , Glicosídeos Cardíacos/uso terapêutico , Contração Miocárdica , Glicosídeos Digitálicos/uso terapêutico , Digoxina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Arritmias Cardíacas , Atropina/uso terapêutico , Doenças Cardiovasculares , Cloreto de Potássio/uso terapêutico , Glicosídeos Digitálicos/biossíntese , Glicosídeos Digitálicos/intoxicação , Relação Dose-Resposta a Droga , Cardioversão Elétrica , Eletrocardiografia , Manifestações Oculares , Hemoperfusão , Lidocaína/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Manifestações Neurológicas , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.