Alkylphosphocholines are phospholipid-like molecules that have been synthesised, which have remarkable biological and therapeutic activities.[1][2] They are phosphocholine esters of aliphatic long chain alcohols differing in chain length, unsaturation and position of the cis-double bond.[3]
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.[4] These analogues function through inhibiting signal transduction pathways of mitosis and triggering apoptosis of cancer cells.[5] Alkylphosphocholine analogues are seen to be more of an efficient treatment for cancer than other drugs as they avoid causing DNA damage and myelotoxicity.[5]
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 with the radioactive isotope iodine-124 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.[6]
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 human RGE cells in vitro, which is one hypothesized way that it is able to impede cell division of human RPE cells.[7]
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 apoptosis.[5]
See also
References
- ^ Unger C, Sindermann H, Peukert M, Hilgard P, Engel J, Eibl H (1992). "Hexadecylphosphocholine in the topical treatment of skin metastases in breast cancer patients". Progress in Experimental Tumor Research. Fortschritte der Experimentellen Tumorforschung. Progrès de la Recherche Expérimentale des Tumeurs. Progress in Tumor Research. 34: 153–9. doi:10.1159/000420840. ISBN 978-3-8055-5464-0. PMID 1438798.
- ^ Zeisig R, Jungmann S, Fichtner I, Daemen T, Arndt D (1994). "Cytotoxic effects of alkylphosphocholines or alkylphosphocholine-liposomes and macrophages on tumor cells". Anticancer Research. 14 (5A): 1785–9. PMID 7847811.
- ^ Dietrich Arndt; Reiner Zeisig; Ines Eue & Iduna Fichtner (1995). "Alkylphosphocholines and Alkylphosphocholine Liposomes". Journal of Liposome Research. 5 (1): 91–98. doi:10.3109/08982109509039910.
- ^ Clark, Paul A.; Al-Ahmad, Abraham J.; Qian, Tongcheng; Zhang, Ray R.; Wilson, Hannah K.; Weichert, Jamey P.; Palecek, Sean P.; Kuo, John S.; Shusta, Eric V. (2016-09-06). "Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood–Brain Barrier Model". Molecular Pharmaceutics. 13 (9): 3341–3349. doi:10.1021/acs.molpharmaceut.6b00441. ISSN 1543-8384. PMC 5014630. PMID 27421304.
- ^ a b c Jendrossek, Verena; Hammersen, Kerstin; Erdlenbruch, Bernhard; Kugler, Wilfried; Krügener, Regina; Eibl, Hansjörg; Lakomek, Max (2002-07-01). "Structure-activity relationships of alkylphosphocholine derivatives: antineoplastic action on brain tumor cell lines in vitro". Cancer Chemotherapy and Pharmacology. 50 (1): 71–79. doi:10.1007/s00280-002-0440-8. ISSN 1432-0843. PMID 12111115. S2CID 25081528.
- ^ Weichert, Jamey P.; Clark, Paul A.; Kandela, Irawati K.; Vaccaro, Abram M.; Clarke, William; Longino, Marc A.; Pinchuk, Anatoly N.; Farhoud, Mohammed; Swanson, Kyle I.; Floberg, John M.; Grudzinski, Joseph (2014-06-11). "Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy". Science Translational Medicine. 6 (240): 240ra75. doi:10.1126/scitranslmed.3007646. ISSN 1946-6234. PMC 4336181. PMID 24920661.
- ^ Eibl, Kirsten H.; Banas, Bernhard; Schoenfeld, Carlo-L.; May, Christian A.; Neubauer, Aljoscha S.; Priglinger, Siegfried; Kampik, Anselm; Welge-Lussen, Ulrich (2003-08-01). "Alkylphosphocholines Inhibit Proliferation of Human Retinal Pigment Epithelial Cells". Investigative Ophthalmology & Visual Science. 44 (8): 3556–3561. doi:10.1167/iovs.02-1172. ISSN 1552-5783. PMID 12882807.
This page was last edited on 11 December 2022, at 19:14