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Keywords = phosphocholine cytidylyltransferase

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14 pages, 3652 KiB  
Article
An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane
by Inmaculada de Dios-Pérez, Álvaro González-Garcinuño and Eva María Martín del Valle
Molecules 2022, 27(9), 2735; https://doi.org/10.3390/molecules27092735 - 24 Apr 2022
Cited by 3 | Viewed by 1929
Abstract
Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the [...] Read more.
Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer. Full article
(This article belongs to the Special Issue Medical Nanocapsules)
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Figure 1

Figure 1
<p>(<b>A</b>) Farnesol formation in mevalonate pathway [<a href="#B5-molecules-27-02735" class="html-bibr">5</a>]; (<b>B</b>) Phosphatidylcholine formation.</p> Full article ">Figure 2
<p>NMR Spectra of SBE-β-CD (<b>B</b>), complex with FOH isomer mixture (<b>C</b>), complex <span class="html-italic">E</span>,<span class="html-italic">E</span>-FOH (<b>D</b>), and its comparative (<b>A</b>).</p> Full article ">Figure 2 Cont.
<p>NMR Spectra of SBE-β-CD (<b>B</b>), complex with FOH isomer mixture (<b>C</b>), complex <span class="html-italic">E</span>,<span class="html-italic">E</span>-FOH (<b>D</b>), and its comparative (<b>A</b>).</p> Full article ">Figure 3
<p>Formation cyclodextrin—drug inclusion complexes [<a href="#B35-molecules-27-02735" class="html-bibr">35</a>].</p> Full article ">Figure 4
<p>Graphical representation of IC50 estimation for FOH (vertically hatched columns), CD (horizontally hatched columns), and the complex (filled columns) in four cancer cell lines (blue—fibroblast, orange—colorectal, pink—breast, green—liver).</p> Full article ">Figure 5
<p>Cell viability results of each cell line treated for 24 h (filled columns) and 48 h (hatched columns).</p> Full article ">Figure 6
<p>Cell viability results for each cell line treated for 24 h in absence (filled columns) or presence (dotted columns) of PC.</p> Full article ">Figure 7
<p>Percentage of cells in G0/G1 phase after treatment of fibroblast and colorectal cancer cells for 24 and 48 h; (<b>A</b>) Concentration of treatments is FOH 150 µM and SBE-β-CD 300 µM; (<b>B</b>) Concentration of treatments is FOH 300 µM and SBE-β-CD 600 µM. (<b>C</b>) Difference in the percentage of cells in G0/G1 phase compared to the control.</p> Full article ">
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