Marine Alkaloid Polycarpine and Its Synthetic Derivative Dimethylpolycarpine Induce Apoptosis in JB6 Cells Through p53- and Caspase 3-Dependent Pathways

Fedorov, Sergey N.; Bode, Ann M.; Stonik, Valentin A.; Горшкова, И. А.; Schmid, Patricia C.; Radchenko, Oleg S.; Berdyshev, Evgueni V.; Dong, Zigang

doi:10.1007/s11095-004-7683-5

Cited by 27 publications

(18 citation statements)

References 44 publications

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“…A plethora of evidence exists that p53 is involved in the chemopreventive effects of many natural compounds. For example resveratrol, epigallocatechin-3-gallate, caffeine, and many other cancer-preventive substances suppress normal cell transformation or induce antiproliferative effects with subsequent apoptosis in cancer cells through a p53-dependent pathway [43,45,[56][57][58][59][60][61][62][63][64][65][66][67]. To explore a possible mechanism of the cancer-preventive action of rhizochalin and analogs, we studied pro-apoptotic properties of rhizochalin and the effect of the compounds 1 or 3 on p53 transcriptional activation in JB6 Cl41 p53 cells stably expressing a luciferase reporter gene controlled by a p53 DNA binding sequence.…”

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

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“…Using flow cytometry and the DNA laddering method, we showed that quinones 1 and 3 -14 induced apoptosis in JB6 Cl41 cells and MEFs. The tumor suppressor protein, p53, which is a part of the cell's emergency team and functions to negatively regulate cell growth following DNA damage, is often involved in apoptosis induced by various stimuli including chemopreventive agents and drugs (41)(42)(43)(44)(45). However, in our study quinones 1 and 3 -14 did not activate p53 but instead, most of the quinones studied demonstrated significant inhibition of p53 dependent transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cancer-Preventive Activity and Structure–Activity Relationships of 3-Demethylubiquinone Q2, Isolated from the Ascidian Aplidium glabrum, and its Synthetic Analogs

et al. 2006

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Purpose-3-Demethylubiquinone Q 2 (1) was isolated from the ascidian Aplidium glabrum. The cancer preventive properties and the structure-activity relationship for 3-demethylubiquinone Q2 (1) and 12 of its synthetic analogues (3-14) are reported.Methods-Compounds 3-14, having one or several di-or triprenyl substitutions and quinone moieties with methoxyls in different positions, were synthesized. The cancer preventive properties of compounds 1 and 3-14 were tested in JB6 Cl41 mouse skin cells, using a variety of assessments, including the MTS assay, flow cytometry, and soft agar assay. Statistical nonparametric methods were used to confirm statistical significance.Results-All quinones tested were shown to inhibit JB6 Cl41 cell transformation, to induce apoptosis, AP-1 and NF-κB activity, and to inhibit p53 activity. The most promising effects were indicated for compounds containing two isoprene units in a side chain and a methoxyl group at the para-position to a polyprenyl substitution.Conclusions-Quinones 1 and 3-14 demonstrated cancer preventive activity in JB6 Cl41 cells, which may be attributed to the induction of p53-independent apoptosis. These activities depended on the length of side chains and on the positions of the methoxyl groups in the quinone part of the molecule.Keywords marine prenylated quinones; cancer prevention; apoptosis; nuclear factor; structure-activity relationship ABBREVIATIONS 3-demethylubiquinone Q2. 2,3-dimethoxy-5-(3′,7′-dimethyl-octa-2′(E),6′-dienyl)- [1,4] benzoquinone (1); EGF, epidermal growth factor; TPA, 12-O-tetradecanoyl-phorbol-13-acetate; FBS, fetal bovine serum; MEM, minimum essential medium

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“…The JB6 P + Cl41 mouse epidermal cell line and its stable transfectants were cultured as described previously (9). The human lung H460, colon HCT-116, and skin melanoma SK-MEL-28 and SK-MEL-5 cancer cell lines were obtained by American Type Culture Collection and were cultured in monolayers at 37jC and 5% CO 2 in RPMI, McCoy's, and MEM, respectively, containing 10% FBS, 2 mmol/L L-glutamine, 100 units/mL penicillin, and 100 Ag/mL streptomycin.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2007

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The marine natural chamigrane-type sesquiterpenoid, dactylone, is closely related to secondary metabolites of some edible species of red algae. In the present study, the effect of dactylone was tested on the mouse skin epidermal JB6 P + Cl41 cell line and its stable transfectants as well as on several human tumor cell lines, including lung (H460), colon (HCT-116), and skin melanomas (SK-MEL-5 and SK-MEL-28). This natural product was effective at nontoxic doses as a cancerpreventive agent, which exerted its actions, at least in part, through the inhibition of cyclin D3 and Cdk4 expression and retinoblastoma tumor suppressor protein (Rb) phosphorylation. The inhibition of these cell cycle components was followed by cell cycle arrest at the G 1 -S transition with subsequent p53-independent apoptosis. Therefore, these data showed that application of dactylone and related compounds may lead to decreased malignant cell transformation and/or decreased tumor cell proliferation. [Cancer Res 2007;67(12):5914-20]

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Marine Alkaloid Polycarpine and Its Synthetic Derivative Dimethylpolycarpine Induce Apoptosis in JB6 Cells Through p53- and Caspase 3-Dependent Pathways

Cited by 27 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

Evaluation of Cancer-Preventive Activity and Structure–Activity Relationships of 3-Demethylubiquinone Q2, Isolated from the Ascidian Aplidium glabrum, and its Synthetic Analogs

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

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Marine Alkaloid Polycarpine and Its Synthetic Derivative Dimethylpolycarpine Induce Apoptosis in JB6 Cells Through p53- and Caspase 3-Dependent Pathways

Cited by 27 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

Evaluation of Cancer-Preventive Activity and Structure–Activity Relationships of 3-Demethylubiquinone Q2, Isolated from the Ascidian Aplidium glabrum, and its Synthetic Analogs

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

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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