Enhanced prostaglandin synthesis as a mechanism for inhibition of melanoma cell growth by ascorbic acid

1988 ◽  
Vol 34 (2) ◽  
pp. 119-126 ◽  
Author(s):  
N.S. Gardiner ◽  
J.R. Duncan
Keyword(s):  
Ascorbic Acid ◽  
Cell Growth ◽  
Melanoma Cell ◽  
Prostaglandin Synthesis

scholarly journals DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity

2020 ◽  
Author(s):  
Daniel J. Wilcock ◽  
Andrew P. Badrock ◽  
Rhys Owen ◽  
Melissa Guerin ◽  
Andrew D. Southam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Melanoma Cell ◽  
Drug Targets ◽  
Lipid Peroxides ◽  
Acid Oxidation ◽  
Growth Factor Signaling ◽  
Bona Fide

ABSTRACTDysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides.SIGNIFICANCEWe show that DGAT1 is a bona fide oncoprotein capable of inducing melanoma formation and co-operating with other known drivers of melanoma. DGAT1 facilitates enhanced fatty acid acquisition by melanoma cells through suppressing lipototoxicity. DGAT1 is also critical for maintaining S6K activity required for melanoma cell growth.

scholarly journals COLLAGEN BIOSYNTHESIS

1957 ◽  
Vol 3 (5) ◽  
pp. 685-695 ◽  
Author(s):  
J. Frederick Woessner ◽  
Bernard S. Gould
Keyword(s):  
Ascorbic Acid ◽  
Cell Growth ◽  
Lung Tissue ◽  
Appreciable Effect ◽  
Collagen Biosynthesis ◽  
Embryonic Lung ◽  
Marked Contrast ◽  
Collagen Formation ◽  
Quantitative Studies ◽  
Total Failure

Quantitative studies of collagen formation by chick embryonic lung tissue grown in media deficient in, or completely lacking, ascorbic acid have been carried out. Cell growth and collagen formation in such cultures can proceed almost normally in media lacking ascorbic acid. Ascorbic acid in combination with whole embryo extract, dialyzed media, or synthetic mixture number 703 was found to have no appreciable effect on cell growth or total collagen formation. This is in marked contrast to the almost total failure of collagen formation in scorbutic animals and suggests that for slow collagen biosynthesis as distinct from more prolific collagen-producing systems, ascorbic acid plays an indirect role.

Synthesis of Thia-Analogous IndirubinN-Glycosides and their Influence on Melanoma Cell Growth and Apoptosis

ChemMedChem ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. 534-539 ◽  
Author(s):  
Manfred Kunz ◽  
Katrin M. Driller ◽  
Martin Hein ◽  
Stephanie Libnow ◽  
Ina Hohensee ◽  
...  
Keyword(s):  
Cell Growth ◽  
Melanoma Cell

4-Methylumbelliferone inhibits tumour cell growth and the activation of stromal hyaluronan synthesis by melanoma cell-derived factors

2010 ◽  
Vol 162 (6) ◽  
pp. 1224-1232 ◽  
Author(s):  
M. Edward ◽  
J.A. Quinn ◽  
S.M. Pasonen-Seppänen ◽  
B.A. McCann ◽  
R.H. Tammi
Keyword(s):  
Cell Growth ◽  
Melanoma Cell ◽  
Tumour Cell ◽  
Tumour Cell Growth

Tacrolimus and ascomycin inhibit melanoma cell growth, migration and invasion via targeting nuclear factor of activated T-cell 3

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Tian Xiao ◽  
Wencong Chen ◽  
Shuangfeng Wang ◽  
Shiying Huang ◽  
Chengyao Chiang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Growth ◽  
Melanoma Cell ◽  
Migration And Invasion ◽  
Nuclear Factor ◽  
Activated T Cell

scholarly journals Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth

Medicines ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 71 ◽  
Author(s):  
Tung-chin Chiang ◽  
Brian Koss ◽  
L. Joseph Su ◽  
Charity L. Washam ◽  
Stephanie D. Byrum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Growth ◽  
Gene Transcription ◽  
Melanoma Cell ◽  
Dna Methyltransferase ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Epigenetic Modifications ◽  
Driving Mechanism ◽  
Epigenetic Drug

Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2’-deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine—C-C motif ligand 5 (CCL-5)—was validated. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth.

scholarly journals Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1

2020 ◽  
Vol 21 (18) ◽  
pp. 6706
Author(s):  
Geon-Hee Kim ◽  
Xue-Quan Fang ◽  
Woo-Jin Lim ◽  
Jooho Park ◽  
Tae-Bong Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Melanoma Cell ◽  
Transcriptional Activity ◽  
Melanoma Cells ◽  
Lung Cancer Cells ◽  
Luciferase Assay ◽  
Dependent Manner

Constitutive activation of the β-catenin dependent canonical Wnt signaling pathway, which enhances tumor growth and progression in multiple types of cancer, is commonly observed in melanoma. LEF1 activates β-catenin/TCF4 transcriptional activity, promoting tumor growth and progression. Although several reports have shown that LEF1 is highly expressed in melanoma, the functional role of LEF1 in melanoma growth is not fully understood. While A375, A2058, and G361 melanoma cells exhibit abnormally high LEF1 expression, lung cancer cells express lower LEF1 levels. A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed β-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression. Cinobufagin decreases LEF1 expression in a dose-dependent manner and Wnt/β-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines. Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells. In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells. Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/β-catenin signaling via LEF1 inhibition.

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