Breaking Through the Membrane’s Wall
Attack on Warwick Castle (Wikicommons licence)
A combination of more-or-less constant war, and the honour of winning it, created a desire for constant improvement to castles built in England in the middle ages. At first they were little more than a place to house soldiers. They rapidly gained status as the centre of local power—at first to protect the local people, and after the Norman invasion, to subdue them. Thus, attacking and taking castles became a way to gain power and destroy enemies. It therefore became useful to be able to break into a castle and destroy or replace the occupants, if not bring down the whole structure. Siege tactics were used sometimes, but impatience or an army equipped for violent attack led to more direct attacks on castles with a view to breaking into them. The latter had a stronger political effect as well as a more immediate shift of power.
There is a similar motivation that exists in the present day. However, these enemies are not the symbols or seats of power of bloodthirsty would-be usurper kings, but are equally fatal. And, like mediaeval fortifications, cancer cells cannot always be defeated by siege methods alone. Sometimes molecular invaders need to break the metaphorical walls of the castle, the cancerous cell’s membrane, in order to over throw the (biological) usurper who will otherwise bring the kingdom down.
There are two ways to do this. Either the biological soldiers (drug molecules) can break in through small and transient holes in the walls (cell membrane), or they can precipitate large-scale destruction of the walls (weaken the membrane so the cell falls apart). Both destroy the integrity of the castle, but in quite different ways.
In fact both of these approaches make good strategies for destroying cancer cells in human bodies. Cancer therapies can either interfere with the membrane such that it no longer provides protection for its cell, or they can be developed so that they pass through it easily and earn their honour by killing the cell from the inside. Exciting recent work from several groups explores both of these approaches, and provides useful basic information for possible future attacks. Neves et al. report evidence for the anti-cancer compound resveratrol interfering with the function of the cell membrane [1] –they change its structure and fluidity. Purushothaman et al. investigated the relationship between the rate at which anti-cancer drug norfloxacin passes through the membrane, and the lipids in that membrane [2]. Future tactics may be informed by work by Dawaliby et al., who have investigated the role of a particular lipid (phosphatidylethanolamine, PE) in directing the physical properties of the cell’s membrane [3]. However, the search is not yet over: much further work is required to understand the membrane perfectly with respect to drug interactions. So, like the Norman and Plantagenet kings in their search for victory and honour, our search for life after cancer, goes on.
References
[1] A. R. Neves, C. Nunes, H. Amenitsch, S. Reis, Soft Matter, 2016, 12, 2118. DOI: 10.1039/c5sm02905h
[2] S. Purushothaman, J. Cama, U. F. Keyser, Soft Matter, 2016, 12, 2135, DOI: 10.1039/c5sm02371h
[3] R. Dawaliby, C. Trubbia, C. Delporte, C. Noyon, J. M. Ruysschaert, P. Van Antwerpen, C. Govaerts, Journal of Biological Chemistry , 2016, 291, 3658–3667. DOI: 10.1074/jbc.M115.706523