Alkylphosphocholines are

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

-like molecules that have been synthesised, which have remarkable biological and therapeutic activities. They are

phosphocholine Phosphocholine is an intermediate in the synthesis of phosphatidylcholine in tissues. Phosphocholine is made in a reaction, catalyzed by choline kinase, that converts ATP and choline into phosphocholine and ADP. Phosphocholine is a molecule ...

esters of aliphatic long chain alcohols differing in chain length, unsaturation and position of the ''cis''-double bond. The utilization of alkylphosphocholine analogues has been found be to useful for the treatment of specific types of cancer, such as gliomas and brain metastases. These analogues function through inhibiting

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

pathways of

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

and triggering

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

of cancer cells. Alkylphosphocholine analogues are seen to be more of an efficient treatment for cancer than other drugs as they avoid causing DNA damage and myelotoxicity.

Research

Analogs of alkylphosphocholines were previously synthesized and shown to have applications in both diagnostic cancer imaging and cancer therapy through in vivo and in vitro experiments. The alkylphosphocoline analog CLR1404 was observed to be selectively absorbed by tumor cells in both human patients with advanced metastatic cancer and mouse models through both

PET imaging Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

with the radioactive isotope

iodine-124 There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element. Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...

as well as through SPECT imaging with the therapeutic radioisotope iodine-131. One of the causes for this selective uptake of CLR1404 was hypothesized to be due to interactions between the analog and lipid rafts of the cancer cell membrane as treatment with the compound filipin III, which disturbs lipid rafts, resulted in less uptake of the alkylphosphocoline analog. Through '' in vitro'' studies, alkylphosphocolines were observed to impede cell division of human retinal pigment epithelium (RPE) cells. This has therapeutic implications on the treatment of proliferative vitreoretinopathy, as this condition can lead to retinal detachment through the abnormal growth and contraction of retinal membranes with RPE cells being significant in facilitating this process. It was experimentally demonstrated that alkylphosphocolines are able to decrease the activity of

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

in human RGE cells in vitro, which is one hypothesized way that it is able to impede cell division of human RPE cells.{{Cite journal , last1=Eibl , first1=Kirsten H. , last2=Banas , first2=Bernhard , last3=Schoenfeld , first3=Carlo-L. , last4=May , first4=Christian A. , last5=Neubauer , first5=Aljoscha S. , last6=Priglinger , first6=Siegfried , last7=Kampik , first7=Anselm , last8=Welge-Lussen , first8=Ulrich , date=2003-08-01 , title=Alkylphosphocholines Inhibit Proliferation of Human Retinal Pigment Epithelial Cells , url=https://iovs.arvojournals.org/article.aspx?articleid=2200230 , journal=Investigative Ophthalmology & Visual Science , language=en , volume=44 , issue=8 , pages=3556–3561 , doi=10.1167/iovs.02-1172 , pmid=12882807 , issn=1552-5783

Erucylphosphocholine

Erucylphosphocholine is an alkylphosphocholine analogue that can be used in the treatment of brain tumors within humans. The usage of the erucylphosphocholine analogue is unique when compared to other alkylphosphocholine analogues because it was the first analogue that has been found to be able to be delivered directly into a patient's veins. This analogue has been found to be useful for the treatment of astrocytoma and glioblastoma cells which are found to be resistant to some methods of chemotherapy. It was found to alter a signaling pathway within the cell cycle and cause tumor cells to enter cell cycle arrest at either the G2 phase or M phase in addition possessing the ability to induce

References

Organophosphates

Research

Erucylphosphocholine

See also

References