Cytotoxicity of the β-carboline alkaloids harmine and harmaline in human cell assays in vitro

Jiménez, J.A Cabrera; Riverón-Negrete, Leticia; Abdullaev, Fikrat I.; Espinosa-Aguirre, J.J.; Rodríguez-Arnáiz, Rosario

doi:10.1016/j.etp.2007.12.003

Cited by 74 publications

(43 citation statements)

References 22 publications

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“…Herraiz confirmed that harmine and harmaline accumulate in dry seeds at 4.3% and 5.6% (w/w), respectively, harmalol at 0.6%, and tetrahydroharmine at 0.1% (w/w) and roots contain harmine and harmol with 2.0% and 1.4% (w/w), respectively (7). Harmaline (dihydro-ß-carboline alkaloid) and harmine (full aromatic ß-carboline alkaloid) are the major alkaloids present in the seeds and the root of P. harmala L. (8) and inhibit monoamine oxidase A (MAO) as a main in-activator of monoaminergic neurotransmitters which is responsible for a number of neurological disorders (7,9). Moreover, harmine showed significant tumor inhibition in mice bearing Lewis Lung Cancer, sarcoma180 or HepA tumor (10).…”

Section: Introductionmentioning

confidence: 99%

Growth Inhibitory Impact of Peganum harmala L. on Two Breast Cancer Cell Lines

et al. 2014

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Background: ß-carbolines, harmaline and harmine, are major alkaloids present in the seeds of Peganum harmala L. These alkaloids are known as herbal active principals with potential use in pharmaceutical and medicine. Objectives: To assess the growth inhibitory effect of phyto-alkaloids, harmaline and harmine, on cancer cell lines. Materials and Methods: P. harmala L.'s alkaloids were extracted by acidic/basic extraction method and identified by two methods, Fourier Transform Infra-Red Spectroscopy (FTIR) and High Performance Liquid Chromatography (HPLC). Two breast cancer cell lines, MDA-MB-231 and Mcf-7, were subjected to different concentrations (1-100 μg.mL -1 ) of the P. harmala extract at different time courses (24, 48, and 72 hours). Methylthiazol Tetrazolium (MTT) test, half maximal inhibitory concentration (IC 50 ) and morphological changes through optical microscopy were evaluated. Results: In both studied cell lines, the P. harmala extract decreased cell viability in longer time exposure in a dose dependent manner. The more concentrated extract led to higher motility of MDA-MB-231 at 24 hours. Although, Mcf-7 cell line required longer exposure time to reach the same motility. It was observed that 30 μg.mL -1 is the minimum lethal dose that kills approximately 50% of cells at 24 hours for MDA-MB-231 cell line (IC 50 ). IC 50 for Mcf-7 was calculated 40 μg.mL -1 and 25 μg.mL -1 48 and 72 hours after being exposed against harmala's extract, respectively. The morphological observation confirmed the apoptosis nature of P. harmala on cells as their membrane kept intact and no membrane permeabilization was observed. Conclusions:The results revealed that the P. harmala extracts significantly decreased the growth rate and cell survival of cancer cell lines. The extract induced cell death regarding natural cell growth rate. MDA-MB-231 cell line naturally has a higher growth rate than Mcf-7 cell line, thus higher growth inhibition of MDA-MB-231 cell line by the P. harmala extract was confirmed.

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Section: Introductionmentioning

confidence: 99%

Growth Inhibitory Impact of Peganum harmala L. on Two Breast Cancer Cell Lines

et al. 2014

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“…Interestingly, harmine was once used as an anti-parkinsonian agent and was soon abandoned for its disappointing effectiveness [6]. Harmine and harmaline showed special affinity to the central nervous system (CNS) and exhibited extensive bioactivities such as multi-enzymes inhibitions including monoamine oxidaze type-A [7,8], cyclin-dependent kinases [9], N-acetyltransferase [10] and Na-K ATPase [11], cytotoxicity and antitumour activities [12,13], anti-bacterial activity [14], antiplasmodial activity [15], antileishmanial activity [16], immunomodulator properties [17], temperature-lowering effect [18], cardiovascular actions [19] and so on. Recent research reported that the alkaloids showed potential inhibitory effects on the acetylcholinesterase (AChE) activity using an in vitro thin-layer chromatography (TLC)-bioautographic assay, and ten alkaloids isolated were evaluated based on their inhibitory ability [20].…”

Section: Introductionmentioning

confidence: 99%

Characterization and determination of trace alkaloids in seeds extracts fromPeganum harmalalinn. Using LC-ESI-MS and HPLC

Liu

Zhao

Cheng

et al. 2013

Acta Chromatographica

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Summary. Harmaline and harmine accounted for more than 70% in composition in extracts of P. harmala. More attention, however, should be paid to the other alkaloids which would be favorable or unfavorable to the efficacy and safety of the products. It was necessary to determine these trace alkaloids in the extracts; thereafter, most of them have been characterized. Diglycoside vasicine, vasicine, vasicinone, harmalol, harmol, tetrahydroharmine, 8-hydroxy-harmine, ruine, harmaline, and harmine were separated and identified with reference substances and characteristic MS spectra in extracts by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and high-performance liquid chromatography (HPLC). Three trace alkaloids, vasicine, harmalol, and harmol were determined using the developed chromatographic separation method subsequently. The average contents of vasicine, harmalol, and harmol in extracts of ten batches were 2.53 ± 0.73, 0.54 ± 0.19, and 0.077 ± 0.03%, respectively. The total content of the three alkaloids was 3.23 ± 0.90% (from 1.81 to 4.48%). For rough estimation of all the relative alkaloids except of harmaline and harmine, the average total areas of all peaks in extracts varied from 4.35 to 26.64% detected at 220, 254, 265, 280, and 380 nm, respectively. The results indicated that area normalization method was powerless for the quality evaluation for traditional herb medicine consisting of numerous compounds with highly differential features. It might be concluded that LC-MS or HPLC could be utilized as a qualitative and quantitative analytical method for quality control of the extracts from seeds of P. harmala L.

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“…Ademais, muitas das classes de metabólitos secundários responsáveis por atividades medicinais e alelopáticas apresentam toxidez a células vegetais e animais (Souza et al, 2003) como a classe dos terpenos (Adams et al, 2011;Gminski et al, 2010), alcalóides (Mulac e Humpf, 2011;Rakba et al, 1999;Jiménez et al, 2008) e antraquinonas (Mueller e Stopper, 1999).…”

Section: Introductionunclassified

Avaliação do potencial fitotóxico de Persea venosa Nees & Mart. (Lauraceae) sobre sementes e plântulas de diferentes espécies cultivadas

Mendes

Casarin

Sperandio

et al. 2013

Rev. bras. plantas med.

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RESUMO:Este estudo objetiva a análise dos efeitos alelopáticos de Persea venosa (paude-andrade) frente a diversas espécies cultivadas. Para os testes, foram utilizados extratos alcoólicos da casca do caule de pau-de-andrade, conforme sua utilização medicinal, em quatro concentrações. A atividade alelopática foi testada frente às cultivares de milho, soja, alface e rabanete. O experimento foi inteiramente casualizado, com quatro repetições de 50 sementes. A análise de cromatografia em camada delgada, utilizando-se sílica como fase estacionária e solventes de diferentes polaridades como fase móvel, foi utilizada para obtenção do perfil fitoquímico, sendo utilizado reveladores específicos para cada classe de metabólitos secundários testada. Observou-se que com o aumento da concentração do extrato de P. venosa, houve o aumento do número de plântulas anormais em todas as cultivares, chegando a percentuais de anormalidade de 100% para milho e soja, 93% para alface e 67,48% para rabanete na concentração de 160 g/L. Ademais, as anormalidades evidenciadas foram predominantes no sistema radicular das plântulas, ocasionando em todos os casos, necrose, truncamento, engrossamento, atrofia e aumento do número de pêlos absorventes. Devido à severidade com que os extratos afetaram o crescimento e a normalidade das plântulas, este estudo evidencia a possibilidade da ocorrência de citotoxicidade por parte da espécie P. venosa, vastamente utilizada na medicina tradicional.Palavras-chave: Planta medicinal, Persea venosa, toxicidade, alelopatia. ABSTRACT: Evaluation of the phytotoxic potential of Persea venosa Ness & Mart. (Lauraceae) on seeds and seedlings of different species grown.This study aims to analyze the allelopathic effects of Persea venosa (pau-de-andrade) on several cultivars. For the tests, we used alcoholic extracts from the bark of pau-de-andrade, according to their medicinal use in four concentrations. The allelopathic activity was tested on different cultivars of corn, soybeans, lettuce and radish. The experiment was completely randomized, with four replications of 50 seeds. The chromatographic analysis of a thin layer, using silica as the stationary phase and solvents of different polarities as the mobile phase, was used to obtain the phytochemical profile, using specific developers to each class of secondary metabolites tested. It was observed that with an increasing concentration of the extract of P. venosa, there was an increase in the number of abnormal seedlings in all cultivars, reaching percentages of abnormality of 100% for corn and soybeans, 93% for lettuce, and 67.48% for radish at a 160 g/L concentration. Furthermore, the evidenced abnormalities were predominant in the seedling root system, causing, in all cases, necrosis, truncation, atrophy and increased number of hairs. Due to the severity with which the extracts affected the growth of seedlings and their normality, this study highlights the possible occurrence of cytotoxicity by the P. venosa species, which is widely used in traditional medicine.

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Cytotoxicity of the β-carboline alkaloids harmine and harmaline in human cell assays in vitro

Cited by 74 publications

References 22 publications

Growth Inhibitory Impact of Peganum harmala L. on Two Breast Cancer Cell Lines

Growth Inhibitory Impact of Peganum harmala L. on Two Breast Cancer Cell Lines

Characterization and determination of trace alkaloids in seeds extracts fromPeganum harmalalinn. Using LC-ESI-MS and HPLC

Avaliação do potencial fitotóxico de Persea venosa Nees & Mart. (Lauraceae) sobre sementes e plântulas de diferentes espécies cultivadas

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