Dactylone Inhibits Epidermal Growth Factor–Induced Transformation and Phenotype Expression of Human Cancer Cells and Induces G1-S Arrest and Apoptosis

Fedorov, Sergey N.; Shubina, Larisa K.; Bode, Ann M.; Stonik, Valentin A.; Dong, Zigang

doi:10.1158/0008-5472.can-06-3723

Cited by 41 publications

(47 citation statements)

References 44 publications

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“…Natural products, including those of marine origin that show cancer-preventive and anticancer properties, attract more and more attention as probable candidates to be used in cancer- preventive or chemotherapeutic anticancer strategies [35][36][37][38][39][40][41][42]. The cancer-preventive effects of the most common natural chemopreventive compounds, such as resveratrol, caffeine, epigallocatechin-3-gallate were established using promotion-sensitive JB6 P ?…”

Section: Discussionmentioning

confidence: 99%

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells

Fedorov¹,

Makarieva²,

Guzii³

et al. 2009

Lipids

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Rhizochalin [(2R,3R,26R,27R)-2,27-diamino-3-hydroxy-26-[(2R,3R,4S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy]octacosan-11-one], an antimicrobial and cytotoxic marine two-headed sphingolipid-like natural product, isolated from the sponge Rhizochalina incrustata, and some related compounds were studied as anticarcinogenic and proapoptotic agents. The corresponding effects were tested on the mouse skin epidermal JB6 P(+) Cl 41 cell line, its stable transfectants, THP-1, HeLa, and SNU-C4 human tumor cells using a variety of assessments, including cell viability (MTS), flow cytometry, anchorage-independent soft agar, and luciferase assays. At 5-10 muM concentrations, rhizochalin was effective as an inhibitor of the malignant transformation of JB6 P(+) Cl 41 cells or colony formation of human tumor cells, which exerted its action, at least in part, through the induction of p53-dependent apoptosis. Structure-activity relationship study showed aglycon of rhizochalin to be the most active while peracetylated aglycon was the least active among the compounds studied.

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Section: Discussionmentioning

confidence: 99%

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells

Fedorov¹,

Makarieva²,

Guzii³

et al. 2009

Lipids

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“…These can be roughly divided into six subgroups, namely: (1) those with a 6,12-epoxy, also known as laurenan-type acetogenins ; (2) those with a 7,13-epoxy, also known as lauthisan-type acetogenins (835)(836)(837)(838)(839)(840)(841)(842)(843)(844)(845)(846)(847)(848)(849)(850)(851); (3) those with a 4,7:6,12-bisepoxy (852-862); (4) those with a 6,12-epoxy and a second epoxy system between C-7 and either C-9, C-10 or C-11 (863)(864)(865)(866)(867)(868)(869); (5) those with a 7,13-epoxy and a second epoxy system between C-6 and either C-9 or C-10 (870-886); and (6) those with a 4,10:9,13-bisepoxy (887-889) functionality. All laurenan-type acetogenins display a (E)-or (Z)-enyne terminus, with the exception of 831-834 that bear a bromoallene moiety.…”

Section: Acetogenins Containing An Eight-membered Cyclic Ether (Oxocamentioning

confidence: 99%

“…A dechloro-hydroxy analogue of hurgadol (32) was found to be weakly cytotoxic against HL-60 and THP-1 leukemia cells with IC 50 values of 102 and 152 μM, respectively [144]. Dactylone (39) was proven effective at non-toxic doses as a cancer preventive agent, initiating early apoptosis in HL-60 and THP-1 cells [144,851].…”

Section: Cytotoxic Activitymentioning

confidence: 99%

The Laurencia Paradox: An Endless Source of Chemodiversity

Harizani

Iοannou

Roussis

2016

Progress in the Chemistry of Organic Natural Products

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Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites.

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“…These natural products have been investigated for the treatment for many cancers (Fedorov et al 2007;Liu et al 2009). Kava, which grows in Pacific Islands, is a natural product that could effectively inhibit cancer cell proliferation and induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression

Zhao

Chao

Wan

et al. 2011

Can. J. Physiol. Pharmacol.

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Novel effective drugs are still urgently needed in the prevention and treatment of oral adenoid cystic carcinoma (ACC). In this study, we have assessed the antitumor potential and molecular mechanisms of flavokawain B (FKB) as a kava chalcone on the ACC-2 cell line in vitro. The results demonstrated that FKB could significantly inhibit the cell proliferation of ACC-2 in a dose-dependent manner that was associated with induced apoptosis and cell cycle G2-M arrest, and the half maximal inhibitory concentration (IC50) of flavokawain-B treatment for 48 h was estimated to be 4.69 ± 0.43 µmol/L. Mechanistically, FKB could induce the release of cytochrome c from mitochondria into the cytosol, and activate the cleavage of caspase-3 and, eventually, the poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner, leading to marked apoptotic effect of ACC-2 cells. The apoptotic action of FKB was associated with the increased expression of proapoptotic proteins: Bim, Bax, Bak and a decreased expression of antiapoptotic Bcl-2. Among them, Bim expression was significantly induced by FKB, and knockdown of Bim expression by short-hairpin RNAs attenuated the inhibitory effect induced by FKB on ACC-2 cells. These results suggest Bim may be one of the potential transcriptional targets, and suggests the potential usefulness of FKB for the prevention and treatment of ACC.Key words: flavokawain B (FKB), apoptosis, Bcl-2, Bim, ACC-2.Résumé : Il existe toujours un besoin urgent de nouveaux médicaments efficaces pour la prévention et le traitement du carcinome adénoïde kystique (CAK). Dans la présente étude, nous avons évalué le potentiel antitumoral et les mécanismes moléculaires du flavokawain B (FKB), une chalcone issue du kava, sur les cellules CAK-2 in vitro. Les résultats ont montré que FKB a pu inhiber considérablement la prolifération des cellules CAK-2 en fonction de la dose administrée, ce qui été associé à l'arrêt du cycle cellulaire en G2-M et à l'induction de l'apoptose, et que la valeur CI 50 après le traitement au flavokawain B pendant 48 heures a été de 4,69 ± 0,43 µmol/L. Du point de vue des mécanismes, FKB a pu induire la libération du cytochrome c des mitochondries dans le cytosol, et activer le clivage de la caspase-3 et de la poly(ADP-ribose) polymé-rase (PARP) de manière dose dépendante, ce qui a eu un effet apoptotique marqué sur les cellules CAK-2. L'action apoptotique de FKB a été associée à la surexpression des protéines pro-apoptotiques Bim, Bax, Bak et à la sous-expression de la Bcl-2 antiapoptotique. FKB a particulièrement augmenté l'expression de Bim, et l'inhibition de cette expression par les petits ARN en épingle à cheveux a atténué l'effet inhibiteur induit par FKB sur les cellules CAK-2. Ces résultats donnent à penser que Bim pourrait être une cible de transcription potentielle et que FKB pourrait être utile pour la prévention et le traitement du CAK.

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Dactylone Inhibits Epidermal Growth Factor–Induced Transformation and Phenotype Expression of Human Cancer Cells and Induces G1-S Arrest and Apoptosis

Cited by 41 publications

References 44 publications

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells

The Laurencia Paradox: An Endless Source of Chemodiversity

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression

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Dactylone Inhibits Epidermal Growth Factor–Induced Transformation and Phenotype Expression of Human Cancer Cells and Induces G1-S Arrest and Apoptosis

Cited by 41 publications

References 44 publications

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P+ Cl41 Cells

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P+ Cl41 Cells

The Laurencia Paradox: An Endless Source of Chemodiversity

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression

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Product

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Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells

Marine Two‐Headed Sphingolipid‐Like Compound Rhizochalin Inhibits EGF‐Induced Transformation of JB6 P⁺ Cl41 Cells