New duo found for two way take-down
Researchers have found a powerful combination that appears to decimate certain resistant tumour cells.
A team from the US has found that a compound for stopping mitochondrial division can overcome tumour cell resistance to a commonly used cancer drug, and that the combination of the two induces rapid and synergistic cell death.
Separately, neither had an effect.
“In our earlier work, we found that blocking production of a protein called Drp1 stopped mitochondria, known as the powerhouses of the cell, from undergoing fission, which is necessary for the cellular division process called mitosis,” said Dr Bennett Van Houten, Professor of Molecular Oncology at the Pittsburgh School of Medicine.
“The loss of this critical mitochondrial protein caused the cells to arrest in mitosis and to develop chromosomal errors, and eventually led the tumour cell into the cell death pathway known as apoptosis.”
The researchers blocked a key protein in breast cancer cells with an agent called mitochondrial division inhibitor-1 (mdivi-1) and found that when mdivi-1 and the cancer drug ‘cisplatin’ were given together, they caused DNA damage, DNA replication stress, and greater than expected apoptosis rates.
The drug combination acted through two independent biochemical pathways that caused the mitochondrial membrane to swell, increasing its permeability and allowing the leak of chemical signals that trigger apoptosis.
"Cisplatin is one of the most widely used cancer drugs today, but some tumours are inherently resistant to it, and many others become resistant, leading to treatment failure,” Dr. Van Houten said.
“In our studies, this combination overcame cisplatin resistance and caused cancer cell death, which is very encouraging.”
The team is testing the effectiveness in a mouse model of ovarian cancer, a disease that often recurs and no longer responds to cisplatin treatment.