Killing malignant mitochondria is one of the most promising approaches in the development of new anticancer drugs. A research team from UK have now synthesized a copper-containing peptide that is readily taken up by mitochondria in breast cancer stem cells, where it effectively induces apoptosis. The study, published in the journal Angewandte Chemie highlights the powerful therapeutic potential of the metallopeptides.
Mitochondria are the power factories of the cells and the central "node" of cell death induction. If their mitochondria are taken off, cells will die through apoptosis. Cancer cells, which have an increased metabolism, not only contain more mitochondria than healthy cells, but also different ones, structurally and functionally. The distinctive features and their decisive role in cell metabolism have made malignant mitochondria a prominent target for new therapeutic compounds. Bio-inorganic chemist Kogularamanan Suntharalingam and his group at King's College, London, UK, explore how mitochondria killing agents can be inserted into the organelles and what damage can be achieved.
Killing mitochondria could be accomplished, for example, by introducing agents to generate reactive oxygen species (ROS). These reactive compounds interfere with several pathways of the mitochondrial metabolism, having maximal impact on the organelle's function. Suntharalingam's group recently proposed the organometallic compound copper(II) phenanthroline as a potent ROS generator with an especially deadly potential for cancer stem cells. However, this special agent must be delivered to its address and shuffled over the outer mitochondrial membrane. A solution would be to make a parcel, for example, by tethering it to a membrane-soluble peptide specific for mitochondria. "Attachment of mitochondrial-penetrating peptides also enables selective and efficient delivery to mitochondria," the authors proposed.
This study highlights the potential of the metallopeptides as both delivery and killing agents, especially for cancer stem cells.