A technology has been developed to kill cancer cells by making artificial protein polymers in cells. The principle is that the synthesized protein polymer damages the mitochondrial membrane of cancer cells and blocks energy supply. Experiments using mice with skin cancer also confirmed such anticancer effects. A green light has been given to the development of new anticancer drugs with low side effects and resistance.
Professor Yu Ja-hyung of UNIST and Professor Kwak Sang-gyu’s team worked with Professor Jin Joon-oh of Yeungnam University to develop a single molecule (monomer) that binds itself inside the mitochondria of cancer cells. Several monomers combine through polymerization to become protein polymers. In normal cells, polymerization does not occur, so only cancer cells can be selected and killed.
Cancer cells have a lot of active oxygen inside the cell. The researchers focused on this and designed the monomer molecular structure. The monomer molecules are designed to be linked by disulfide bonds. Disulfide bonds are bonds that do not easily decompose within mitochondria of cancer cells with a lot of free oxygen.
The synthesized small-sized protein polymer attacks the mitochondrial membrane, causing oxidative stress, and the free oxygen generated at this time further promotes disulfide bonding to form a large protein polymer. In other words, it is a virtuous cycle system.
These macromolecules simultaneously attack the mitochondrial membrane, destroying the mitochondrial membrane and killing cancer cells. Mitochondria located inside cells are organs that supply energy to cells.
The research team also proved this by animal testing. As a result of direct injection of the monomer material into the skin cancer (SCC7) tissue of mice, the tumor size was reduced to less than half within three weeks.
The research team said the method developed this time is a method of controlling the fate of cells by generating protein mimetic substances within cells, which is expected to lead to the development of various disease treatments as well as cancer treatments. Research support was provided through the Korea Research Foundation, the Ministry of Science and ICT, and the National Supercomputing Center.
Reference: Kim, S., Jana, B., Go, E. M., Lee, J. E., Jin, S., An, E. K., Hwang, J., Sim, Y., Son, S., Kim, D., Kim, C., Jin, J. O., Kwak, S. K., & Ryu, J. H Intramitochondrial Disulfide Polymerization Controls Cancer Cell Fate. ACS Nano, 15(9), 14492–14508. https://doi.org/10.1021/acsnano.1c04015