‘Natural product’ breaks cancer cell membranes
Anticancer compound from a fungus is a promising candidate against a notoriously difficult type of brain tumour.
Many of the medications that are available to treat cancer are either collected from natural sources or inspired by molecules existing in nature. While it is often challenging to understand how these natural compounds selectively kill cancer cells, characterising these mechanisms is essential if researchers are to develop new anticancer drugs and treatments based on these compounds.
Ophiobolin A is a compound naturally made by a fungus in order to attack plant cells. It is also able to potently kill cancer cells from humans. In particular, ophiobolin A is a promising candidate for treatment of a type of brain tumour called glioblastomas, which are notoriously difficult to treat with existing medications.
Using a newly developed method, Christopher Chidley and co-workers have now tested which components of human cancer cells are important for ophiobolin A to exert its killing effect. The method revealed that ophiobolin A was less able to kill cancer cells if the cells had lower levels of a molecule called phosphatidylethanolamine in their surface membranes. This observation led Chidley and co-workers to show that ophiobolin A enters the membrane of human cancer cells and combines chemically with phosphatidylethanolamine to form a new composite molecule. Further experiments showed that the formation of this composite molecule disrupted a model membrane, which suggests that ophiobolin A kills cancer cells by breaking their membranes.
The next challenge is to understand exactly how the composite molecule kills cancer cells via membrane disruption. It also remains unclear if the anticancer activity of ophiobolin A results from cancer cells having a membrane composition that is different from normal cells, and why this difference arises in the first place.
To find out more
Read the eLife research paper on which this eLife digest is based: “The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine” (July 12, 2016).
