The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells

Möller, Maren; Herzer, Kerstin; Wenger, Till; Herr, Ingrid

doi:10.3892/or.18.3.737

Cited by 36 publications

(40 citation statements)

References 20 publications

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“…The alkaloid emetine (12) presented cytotoxic and apoptosis effects in leukemia cell lines via mitochondrial pathway. 56,115 When tested with cisplatin (standard chemotherapeutic agent) it increased levels of apoptosis, inducing the expression of several proapoptotic genes and inhibiting expression of survival factors. 56 The alkaloid psychotripine (23), a trimeric pyrroloindoline derivative with a hendecacyclic system bearing a hexahydro-1,3,5-triazine unit, was isolated from the leaves of P. pilifera.…”

Section: Cytotoxic Activitymentioning

confidence: 99%

The GenusPsychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties

Calixto¹,

Pinto²,

Ramalho³

et al. 2016

Journal of the Brazilian Chemical Society

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Psychotria genus (Rubiaceae) is featured into the angiosperm, being the most speciose genus comprising approximately 1600 species. The available references demonstrate that Psychotria has several uses on traditional medicine including spiritual and cultural purposes, and presents great potential on pharmacological properties, especially the one related to neurodegenerative diseases. Despite its wide biological properties, this genus has shown complex phylogenetic analysis due to lack of chemotaxonomic information. In recent years, the interest in these plants has increased considerably and many active compounds have been isolated. Phytochemical investigations described in the literature confirmed the indole alkaloids as the major compounds and besides that, another particular chemical constituent are cyclic peptides, known as cyclotides. This present review will cover the relevant literature from 1962 until 2015, and outlines the current data on taxonomy, chemotaxonomy, traditional uses, pharmacological properties, chemical composition and ecological approach from Psychotria genus.

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Section: Cytotoxic Activitymentioning

confidence: 99%

The GenusPsychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties

Calixto¹,

Pinto²,

Ramalho³

et al. 2016

Journal of the Brazilian Chemical Society

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“…EME is the hydrochloride of an alkaloid found in the ipecac root and has been known to inhibit protein and nucleic acid syntheses. [25][26][27] Using the SYBR Green-based assay as the secondary assay, we determined the 50% inhibitory concentration (IC 50 ) of CQ, EME, pentamidine isethionate salt, E-64, and bestatin hydrochloride, which were 59.8, 69.0, 68.5, 10,755, and 36,924 nM ( Fig. 5A-E).…”

Section: Confirmation Of the Hits In The Secondary Assaymentioning

confidence: 99%

Validating a Firefly Luciferase-Based High-Throughput Screening Assay for Antimalarial Drug Discovery

Che

Cui

Kutsch

et al. 2012

ASSAY and Drug Development Technologies

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The emergence and spread of multidrug-resistant Plasmodium falciparum and recent detection of potential artemisinin-resistant strains in Southeast Asia highlight the importance of developing novel antimalarial therapies. Using a previously generated stable transgenic P. falciparum line with high-level firefly luciferase expression, we report the adaptation, miniaturization, optimization, and validation of a highthroughput screening assay in 384-well plates. Assay conditions, including the percentage of parasitemia and hematocrit, were optimized. Parameters of assay robustness, including Z 0 -value, coefficient variation (CV), and signal-to-background (S/B) ratio, were determined. The LOPAC 1280 small-compound library was used to validate this assay. Our results demonstrated that this assay is robust and reliable, with an average Z 0 -value of >0.7 and CV of <10%. Moreover, this assay showed a very low background, with the S/B ratio up to 71. Further, identified hits were selected and confirmed using a SYBR Green I-based confirmatory assay. It is evident that this assay is suitable for large-scale screening of chemical libraries for antimalarial drug discovery.

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“…Six compounds were found to inhibit luciferase expression by Ͼ75% and reduce cell viability by Ͻ25% (Table 2). Cephaeline and emetine are closely related alkaloid components of ipecac (19) (a wellknown substance used to induce vomiting), and emetine has been shown to inhibit protein synthesis and promote apoptosis in mammalian cells (3,9,13). Emetine appears to be an especially potent inhibitor of translation of viral mRNA in some systems (16).…”

Section: Fig 2 Establishment Of Ebolavirus Minireplicon Assays For mentioning

confidence: 99%

Minigenome-Based Reporter System Suitable for High-Throughput Screening of Compounds Able To Inhibit Ebolavirus Replication and/or Transcription

Jasenosky

Neumann

Kawaoka

2010

Antimicrob Agents Chemother

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We describe an Ebolavirus minigenome-based system that is suitable for high-throughput screening of compounds able to impair Ebolavirus virus replication and/or transcription. The assay is robust (Z factor, >0.6) and can be carried out in low-biosafety containment. Results from a pilot screen of 960 compounds are presented.Ebolaviruses and the closely related Marburgviruses cause hemorrhagic fever in humans and nonhuman primates, with high mortality rates (18). Currently, treatment of these infections is limited to supportive care (1). The need for efficacious therapeutics is further underscored by the increasing frequency of Ebolavirus outbreaks in both humans and endangered great ape populations (2,20,21).High-throughput screening (HTS) systems should be robust with high reproducibility and should be amenable to work in low-biosafety containment. Ebolavirus is categorized as a biosafety level 4 agent, and HTS systems that rely on live Ebolavirus are thus impractical. Here, we describe a minireplicon system to screen for compounds that interfere with viral replication and/or transcription. In these systems, a virus-like RNA encoding a reporter protein is amplified by the viral proteins required for replication and transcription, i.e., the Ebolavirus polymerase (L), nucleoprotein (NP), and VP30 and VP35 proteins (10,14).A minireplicon system based on Zaire Ebolavirus developed in our laboratory was taken as a starting point (22). First, we generated a reporter construct (p3E5E-Luc) in which the open reading frame (ORF) for the luciferase gene (in antisense orientation) is flanked by the Zaire Ebolavirus leader and trailer regions (which contain the viral promoters for replication and transcription) and by T7 RNA promoter and terminator sequences (Fig. 1A). Next, we transfected human embryonic kidney (293T) cells with p3E5E-Luc, pC-T7 (for T7 polymerase expression [15]), and pCEZ-NP, pCEZ-VP35, pCEZ-VP30, and pCEZ-L (for the expression of the Zaire Ebolavirus NP, VP35, VP30, and L proteins, respectively [15]) using Trans-IT LT1 reagent (Mirus); the amounts of the respective plasmids are listed in Table 1, Setup number 1. To determine background expression levels of luciferase in the absence of a functional nucleocapsid complex (negative control), we substituted empty vector for pCEZ-L. Forty-eight hours posttransfection, an equal volume of Steady-Glo luciferase assay substrate (Promega) was mixed with each sample and luminescence was measured. Mean luciferase expression and standard deviations were obtained by measuring luminescence in eight separate wells for both the positive (with pCEZ-L) and negative (without pCEZ-L) controls. For this and all subsequent experiments, we next calculated the ZЈ factor (24) as a measure of the robustness of the assay:, where p is the standard deviation of the positive control (reporter protein expression from the minireplicon), n is the standard deviation of the negative control (reporter protein expression in the absence of the L protein), p is the mean of the positive control...

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The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells

Cited by 36 publications

References 20 publications

The GenusPsychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties

The GenusPsychotria: Phytochemistry, Chemotaxonomy, Ethnopharmacology and Biological Properties

Validating a Firefly Luciferase-Based High-Throughput Screening Assay for Antimalarial Drug Discovery

Minigenome-Based Reporter System Suitable for High-Throughput Screening of Compounds Able To Inhibit Ebolavirus Replication and/or Transcription

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