The effect of Amaryllidaceae alkaloids haemanthamine and haemanthidine on cell cycle progression and apoptosis in p53-negative human leukemic Jurkat cells

Havelek, Radim; Seifrtová, Martina; Královec, Karel; Brůčková, Lenka; Cahlíková, Lucie; Dalecká, Markéta; Vávrová, Jiřina; Řezáčová, Martina; Opletal, Lubomı́r; Bı́lková, Zuzana

doi:10.1016/j.phymed.2013.09.005

Cited by 64 publications

(60 citation statements)

References 31 publications

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“…Moreover, these molecules are of pharmaceutical interest either as potential anti-tumor agents or for the symptomatic treatment of Alzheimer disease (1,2,4,28). Although the general chemical steps in the core Amaryllidaceae alkaloid biosynthetic pathway have been established (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…These plants produce a group of alkaloids with a range of potential pharmaceutical uses. Of the Amaryllidaceae alkaloids, galanthamine has been used clinically for treatment of Alzheimer disease symptoms (1,2). In addition to galanthamine, the chemically diverse Amaryllidaceae alkaloids have many documented pharmacological activities (3).…”

mentioning

confidence: 99%

“…In addition to galanthamine, the chemically diverse Amaryllidaceae alkaloids have many documented pharmacological activities (3). For example, several have cancer fighting potential including hemanthamine, crinine, and lycorine (2,4,5). Continued development of Amaryllidaceae alkaloids for clinical and pharmaceutical applications requires the establishment of a cost effective production system for these molecules; however, limited information about the genes and proteins involved in the biosynthesis of Amaryllidaceae alkaloids is available.…”

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confidence: 99%

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Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities

Kilgore

Holland

Jez

et al. 2016

Journal of Biological Chemistry

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Amaryllidaceae alkaloids are a large group of plant natural products with over 300 documented structures and diverse biological activities. Several groups of Amaryllidaceae alkaloids including the hemanthamine-and crinine-type alkaloids show promise as anticancer agents. Two reduction reactions are required for the production of these compounds: the reduction of norcraugsodine to norbelladine and the reduction of noroxomaritidine to normaritidine, with the enantiomer of noroxomaritidine dictating whether the derivatives will be the crinine-type or hemanthamine-type. It is also possible for the carbon-carbon double bond of noroxomaritidine to be reduced, forming the precursor for maritinamine or elwesine depending on the enantiomer reduced to an oxomaritinamine product. In this study, a short chain alcohol dehydrogenase/reductase that co-expresses with the previously discovered norbelladine 4-Omethyltransferase from Narcissus sp. and Galanthus spp. was cloned and expressed in Escherichia coli. Biochemical analyses and x-ray crystallography indicates that this protein functions as a noroxomaritidine reductase that forms oxomaritinamine from noroxomaritidine through a carbon-carbon double bond reduction. The enzyme also reduces norcraugsodine to norbelladine with a 400-fold lower specific activity. These studies identify a missing step in the biosynthesis of this pharmacologically important class of plant natural products.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities

Kilgore

Holland

Jez

et al. 2016

Journal of Biological Chemistry

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“…Treatment of cells with both compounds caused the accumulation of cells at G1 and G2 phases of the cell cycle. They also upregulated the expression of p16 and Chk1 Ser345 phosphorylation (Havelek et al 2014). Lin et al (2013) reported that Capsaicin caused apoptosis and cell cycle arrest at G2/M phase in KB cancer cells.…”

Section: Phytoconstituents As Cell Cycle Inhibitorsmentioning

confidence: 97%

Phytoconstituents as apoptosis inducing agents: strategy to combat cancer

et al. 2015

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Advancement in the field of cancer molecular biology has aided researchers to develop various new chemopreventive agents which can target cancer cells exclusively. Cancer chemopreventive agents have proficiency to inhibit, reverse and delay process of carcinogenesis during its early and later course. Chemopreventive agents can act as antioxidative, antimutagenic/antigenotoxic, anti-inflammatory agents or via aiming various molecular targets in a cell to induce cell death. Apoptosis is a kind of cell death which shows various cellular morphological alterations such as cell shrinkage, blebbing of membrane, chromatin condensation, DNA fragmentation, formation of apoptotic bodies etc. Nowadays, apoptosis is being one of the new approaches for the identification and development of novel anticancer therapies. For centuries, plants are known to play part in daily routine from providing food to management of human health. In the last two decades, diverse phytochemicals and various botanical formulations have been characterized as agents that possess potential to execute cancer cells via inducing apoptosis. Data obtained from the research carried out globally pointed out that natural products are the potential candidates which have capability to combat cancer. In the present review, we surveyed literature on natural products which throws light on the mechanism through which these phytochemicals induce apoptosis in cancer cells.

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“…Another Amaryllidaceae alkaloid called lycorine has been shown to arrest the cell cycle and induce apoptosis in the cancer cell line HL-60 (Liu et al, 2004). In addition, the Amaryllidaceae alkaloids haemanthamine and haemanthidine have been shown to have anticancer activities (Havelek et al, 2014; Doskočil et al, 2015). The Amaryllidaceae alkaloids and their derivatives have been a source of novel acetylcholine esterase inhibitors, anti-cancer compounds, anti-viral compounds, and antibacterial compounds.…”

Section: Amaryllidaceae Alkaloidsmentioning

confidence: 99%

The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery

Kilgore

Kutchan

2015

Phytochem Rev

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Amaryllidaceae alkaloids are an example of the vast diversity of secondary metabolites with great therapeutic promise. The identification of novel compounds in this group with over 300 known structures continues to be an area of active study. The recent identification of norbelladine 4′-O-methyltransferase (N4OMT), an Amaryllidaceae alkaloid biosynthetic enzyme, and the assembly of transcriptomes for Narcissus sp. aff. pseudonarcissus and Lycoris aurea highlight the potential for discovery of Amaryllidaceae alkaloid biosynthetic genes with new technologies. Recent technical advances of interest include those in enzymology, next generation sequencing, genetic modification, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS).

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The effect of Amaryllidaceae alkaloids haemanthamine and haemanthidine on cell cycle progression and apoptosis in p53-negative human leukemic Jurkat cells

Cited by 64 publications

References 31 publications

Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities

Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities

Phytoconstituents as apoptosis inducing agents: strategy to combat cancer

The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery

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