RESUMEN
Harmine (HM) is a ßcarboline alkaloid found in multiple medicinal plants. It has been used in folk medicine for anticancer therapy; however, the molecular mechanism of HM on human breast cancer remains unclear. Transcriptional coactivator with PDZbinding motif (TAZ), also known as WW domaincontaining transcription regulator 1, serves an important role in the carcinogenesis and progression of breast cancer. The aim of the present study was to elucidate the potential anticancer activity and mechanism of HM in breast cancer, in vitro and in vivo. Cell proliferation was measured using a CCK8 assay, apoptotic activity was detected by flow cytometry and DAPI staining, and cell migration was examined using a wound healing assay. The expression of proteins, including extracellular signalregulate kinase (Erk), phosphorylated (p) Erk, protein kinase B (Akt), pAkt, Bcell lymphoma 2 (Bcl2) and Bcl2associated X protein (Bax), were determined by western blotting. The mRNA expression of TAZ was detected using reverse transcriptionquantitative polymerase chain reaction analysis. The expression of proteins in mouse tumor tissues were examined by immunohistochemistry. HM significantly suppressed cellular proliferation and migration, promoted apoptosis in vitro and inhibited tumor growth in vivo. In addition, HM significantly decreased the expression of TAZ, pErk, pAkt and Bcl2, but increased that of Bax. The overexpression of TAZ in breast cancer cells inhibited the antitumor effect of HM. In conclusion, HM was found to induce apoptosis and prevent the proliferation and migration of human breast cancer cell lines, possibly via the downregulation of TAZ.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Harmina/administración & dosificación , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Harmina/farmacología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Células MCF-7 , Transducción de Señal/efectos de los fármacos , Transactivadores , Factores de Transcripción , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Harman and norharman, two neuroactive ß-carbolines, are present in several plants and in thermally processed foods. They exhibited a wide spectrum of biological and pharmacological effects, including antioxidant, neuroprotective, and anti-inflammatory effects. In this article, we review the progress of recent research on the presence of these compounds in food, as well as their various biological and neuroactive properties. Our findings strongly suggest that some foods, especially coffee, can act as a rich source of ß-carbolines, which may possibly be associated with a reduced risk for serious neurodegenerative diseases, such as Parkinson's and Alzheimer's.
Asunto(s)
Carbolinas/análisis , Alimentos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Química Encefálica , Carbolinas/administración & dosificación , Carbolinas/química , Carbolinas/farmacología , Temblor Esencial/inducido químicamente , Temblor Esencial/metabolismo , Manipulación de Alimentos , Harmina/administración & dosificación , Harmina/análogos & derivados , Harmina/análisis , Humanos , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Extractos Vegetales/químicaRESUMEN
The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.
Asunto(s)
Ansiedad/tratamiento farmacológico , Banisteriopsis/química , Trastorno Depresivo/tratamiento farmacológico , Pánico/efectos de los fármacos , Extractos Vegetales/farmacología , Adulto , Ansiedad/psicología , Bebidas , Brasil , Trastorno Depresivo/psicología , Método Doble Ciego , Femenino , Frutas/química , Harmalina/administración & dosificación , Harmalina/química , Harmalina/farmacología , Harmina/administración & dosificación , Harmina/análogos & derivados , Harmina/química , Harmina/farmacología , Humanos , Masculino , Persona de Mediana Edad , Estructura Molecular , N,N-Dimetiltriptamina/administración & dosificación , N,N-Dimetiltriptamina/química , N,N-Dimetiltriptamina/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Hojas de la Planta/química , Psicometría/métodos , Religión , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
beta-carboline alkaloids are found in several medicinal plants and display a variety of actions on the central nervous, muscular and cardiovascular systems. The aim of the present study was to evaluate the effects of systemic administration of beta-carboline alkaloids on object recognition in mice. Adult Swiss mice received an intra-peritoneal injection (i.p.) of alkaloids (1.0, 2.5 or 5.0 mg/kg) 30 min before training in an object recognition task. The fully aromatic beta-carbolines, harmine and harmol, induced an enhancement of short-term memory (STM) at all doses tested when compared to controls. Harmaline, a dihydro beta-carboline and inverse agonist of the MK-801 binding site on the N-methyl-d-aspartate (NMDA) receptor, also induced an enhancement of both short-term memory (STM) and long-term memory (LTM). These results demonstrate that systemic administration of beta-carboline alkaloids can improve object recognition memory in mice.
Asunto(s)
Alcaloides/farmacología , Carbolinas/farmacología , Harmalina/farmacología , Harmina/farmacología , Reconocimiento en Psicología/fisiología , Alcaloides/administración & dosificación , Animales , Carbolinas/administración & dosificación , Harmalina/administración & dosificación , Harmina/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Ratones , Modelos Animales , Reconocimiento en Psicología/efectos de los fármacosRESUMEN
Although it has been known for many years that hallucinogenic drugs are used by witch doctors in the Peruvian jungles for therapeutic purposes, there have been no descriptions of their use. We studied one type of treatment carried out in groups of about 10 to 12 'patients', where the healer makes a magical diagnosis and provides a potion, usually ayahuasca (active hallucinogenic agent: harmine) which is drunk by the witch doctor, his assistant and the patients. The groups meet one a week in the open air in the jungle, at dawn and for an average of 5 h. The patient attends the weekly sessions until he feels well enough to leave, and only then does he pay a voluntary fee. One of our main tasks was to study the group processes.