This work may open a new approach to attacking cancer. Credit: skeeze, (CCO)]
This work may open a new approach to attacking cancer. Credit: skeeze, (CCO)]

Cancer cells watch out. A new way to fight cancer works by disrupting mitochondria, crucial energy-generating structures inside cells. “We hope our work will inspire the development of new anti-cancer drugs for precise and efficient therapy,” says Xian-Zheng Zhang, who was part of the research team at Wuhan University, China. The results are reported in the journal Materials Today Chemistry.

"Traditionally, the therapeutic targets of anti-cancer agents have been the DNA or proteins within cancer cells,” says Zhang. Instead, his work uses "ethidium derivative" compounds to initiate a cascade of molecular events affecting cancer cells’ mitochondria. These include a reduction in the production of ATP, the key energy currency within cells, destroying the normal electrochemical balance within the mitochondria and releasing a key component of the programmed cell death (apoptosis) system called cytochrome C. Without properly functioning mitochondria, cells cannot produce energy and so eventually die.

The ability to specifically target mitochondria was a rather unexpected discovery. “To our surprise, we found the molecules were selectively diverted into the mitochondria of cancer cells,” says Zhang. They had originally been expected to accumulate in a cell’s nucleus and bind to its DNA, since they contain a structural feature known to have DNA-binding properties.

Along with precision, their attack has an additional advantage of helping diagnosis. This is known as a “theranostics” capability – therapy and diagnostics combined. This stems from a fluorescent tag built into the molecules that lights up cancer cells, thereby helping to locate the cancer and also monitor the progress of treatment.

The researchers believe that their molecules have the potential to “present a new paradigm for developing unique anti-cancer theranostic agents.” By showing that it is possible to disrupt mitochondria, other researchers will start looking at that option too.

The team have already observed good cell-killing and anti-proliferation activity in cells. Additionally, they have uncovered many chemical details of the molecular mechanisms behind the anti-cancer effects. This understanding should help work to refine the therapeutic effects and also to develop other related and perhaps even more effective compounds.

They have also done trials with mice with cancer, which has shown the molecules are effective cancer fighters, with no obvious undesirable side effects. After 13 days of treatment by drug injection, the mice had tumor masses that were 35% or less of the mass of those tumors in untreated mice. Further research is needed to explore if this suppression of cancer can be continued and improved upon. The promise of fighting cancer while perhaps leaving healthy cells undamaged could avoid the “collateral damage” to healthy tissue that complicates and limits the use of many anti-cancer treatments.

Zhang hopes to move to clinical trials with people with cancer in the future. Before reaching that stage, the effects of higher doses in animals need to be studied, and followed for longer times, while looking out for damaging side effects. The early results suggest Zhang and his colleagues may have found a promising new treatment and diagnostic tool.

Zhang, Xian-Zheng et al.: "Mitochondria targeted cancer therapy using ethidium derivatives," Materials Today Chemistry (2017)