Effects of Paclitaxel on Plasma Membrane Microviscosity and Lipid Composition in Cancer Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Aug 12

PMID 37569560

Authors

Liubov Shimolina

Alexander Gulin

Alexandra Khlynova

Nadezhda Ignatova

Irina Druzhkova

Margarita Gubina

Elena Zagaynova

Marina K Kuimova

Marina Shirmanova

Affiliations

Soon will be listed here.

Abstract

The cell membrane is an important regulator for the cytotoxicity of chemotherapeutic agents. However, the biochemical and biophysical effects that occur in the membrane under the action of chemotherapy drugs are not fully described. In the present study, changes in the microviscosity of membranes of living HeLa-Kyoto tumor cells were studied during chemotherapy with paclitaxel, a widely used antimicrotubule agent. To visualize the microviscosity of the membranes, fluorescence lifetime imaging microscopy (FLIM) with a BODIPY 2 fluorescent molecular rotor was used. The lipid profile of the membranes was assessed using time-of-flight secondary ion mass spectrometry ToF-SIMS. A significant, steady-state decrease in the microviscosity of membranes, both in cell monolayers and in tumor spheroids, was revealed after the treatment. Mass spectrometry showed an increase in the unsaturated fatty acid content in treated cell membranes, which may explain, at least partially, their low microviscosity. These results indicate the involvement of membrane microviscosity in the response of tumor cells to paclitaxel treatment.

References

Bernsdorff C, Reszka R, Winter R . Interaction of the anticancer agent Taxol (paclitaxel) with phospholipid bilayers. J Biomed Mater Res. 1999; 46(2):141-9. DOI: 10.1002/(sici)1097-4636(199908)46:2<141::aid-jbm2>3.0.co;2-u. View

Carvalho A, Fernandes E, Goncalves H, Giner-Casares J, Bernstorff S, Nieder J . Prediction of paclitaxel pharmacokinetic based on in vitro studies: Interaction with membrane models and human serum albumin. Int J Pharm. 2020; 580:119222. DOI: 10.1016/j.ijpharm.2020.119222. View

Duportail G, Coupin G, Kuhry J . The influence of microtubule integrity on plasma membrane fluidity in L929 cells. Mol Membr Biol. 2000; 17(2):95-100. DOI: 10.1080/09687680050117110. View

Shimolina L, Gulin A, Ignatova N, Druzhkova I, Gubina M, Lukina M . The Role of Plasma Membrane Viscosity in the Response and Resistance of Cancer Cells to Oxaliplatin. Cancers (Basel). 2021; 13(24). PMC: 8699340. DOI: 10.3390/cancers13246165. View

Zhao L, Feng S . Effects of lipid chain unsaturation and headgroup type on molecular interactions between paclitaxel and phospholipid within model biomembrane. J Colloid Interface Sci. 2005; 285(1):326-35. DOI: 10.1016/j.jcis.2004.11.032. View

Dhanikula A, Panchagnula R . Fluorescence anisotropy, FT-IR spectroscopy and 31-P NMR studies on the interaction of paclitaxel with lipid bilayers. Lipids. 2008; 43(6):569-79. DOI: 10.1007/s11745-008-3178-1. View

Peetla C, Vijayaraghavalu S, Labhasetwar V . Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles. Adv Drug Deliv Rev. 2013; 65(13-14):1686-98. PMC: 3840112. DOI: 10.1016/j.addr.2013.09.004. View

Kang M, Loverde S . Molecular simulation of the concentration-dependent interaction of hydrophobic drugs with model cellular membranes. J Phys Chem B. 2014; 118(41):11965-72. DOI: 10.1021/jp5047613. View

Ashrafuzzaman M, Tseng C, Duszyk M, Tuszynski J . Chemotherapy drugs form ion pores in membranes due to physical interactions with lipids. Chem Biol Drug Des. 2012; 80(6):992-1002. DOI: 10.1111/cbdd.12060. View

10.

McGrail D, Khambhati N, Qi M, Patel K, Ravikumar N, Brandenburg C . Alterations in ovarian cancer cell adhesion drive taxol resistance by increasing microtubule dynamics in a FAK-dependent manner. Sci Rep. 2015; 5:9529. PMC: 4400875. DOI: 10.1038/srep09529. View

11.

Shimolina L, Gulin A, Khlynova A, Ignatova N, Druzhkova I, Gubina M . Development of resistance to 5-fluorouracil affects membrane viscosity and lipid composition of cancer cells. Methods Appl Fluoresc. 2022; 10(4). DOI: 10.1088/2050-6120/ac89cd. View

12.

Shirmanova M, Shimolina L, Lukina M, Zagaynova E, Kuimova M . Live Cell Imaging of Viscosity in 3D Tumour Cell Models. Adv Exp Med Biol. 2017; 1035:143-153. DOI: 10.1007/978-3-319-67358-5_10. View

13.

Ganguly A, Cabral F, Yang H, Patel K . Peloruside A is a microtubule-stabilizing agent with exceptional anti-migratory properties in human endothelial cells. Oncoscience. 2015; 2(6):585-95. PMC: 4506362. DOI: 10.18632/oncoscience.169. View

14.

BERLIN R, Fera J . Changes in membrane microviscosity associated with phagocytosis: effects of colchicine. Proc Natl Acad Sci U S A. 1977; 74(3):1072-6. PMC: 430595. DOI: 10.1073/pnas.74.3.1072. View

15.

Menendez J, Lupu R, Colomer R . Exogenous supplementation with omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells. Eur J Cancer Prev. 2005; 14(3):263-70. DOI: 10.1097/00008469-200506000-00011. View

16.

Ji X, Lu Y, Tian H, Meng X, Wei M, Cho W . Chemoresistance mechanisms of breast cancer and their countermeasures. Biomed Pharmacother. 2019; 114:108800. DOI: 10.1016/j.biopha.2019.108800. View

17.

Aszalos A, Yang G, Gottesman M . Depolymerization of microtubules increases the motional freedom of molecular probes in cellular plasma membranes. J Cell Biol. 1985; 100(5):1357-62. PMC: 2113863. DOI: 10.1083/jcb.100.5.1357. View

18.

Peetla C, Bhave R, Vijayaraghavalu S, Stine A, Kooijman E, Labhasetwar V . Drug resistance in breast cancer cells: biophysical characterization of and doxorubicin interactions with membrane lipids. Mol Pharm. 2010; 7(6):2334-48. PMC: 2997943. DOI: 10.1021/mp100308n. View

19.

McDermott M, Eustace A, Busschots S, Breen L, Crown J, Clynes M . In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies. Front Oncol. 2014; 4:40. PMC: 3944788. DOI: 10.3389/fonc.2014.00040. View

20.

Chavez J, Keller A, Zhou B, Tian R, Bruce J . Cellular Interactome Dynamics during Paclitaxel Treatment. Cell Rep. 2019; 29(8):2371-2383.e5. PMC: 6910234. DOI: 10.1016/j.celrep.2019.10.063. View