If you can't attack a cancer cell directly, attack its DNA. Then prevent its DNA from repairing itself. That's the direction scientists from Georgetown University Medical Center have undertaken in the development of a new anti-cancer therapy.
The researchers have forged the bullets in their new gun from an unlikely material: synthetic versions of strigolactones, plant hormones normally made organically in roots that regulate development of plant roots under ground and shoots above ground.
The scientists have been working with the synth-strigolactones – known as MEB55 and ST362 – since 2009, and have led a series of studies showing that synthetic versions of strigolactones can shut down cancer growth in breast, prostate, colon, lung and a variety of other tumor cells. Their latest work shows the mechanisms of the plant hormone and how it can be used to kill in human prostate cancer cells when combined with another cancer drug.
“MEB55 and ST362 appear to be very promising agents. Our study suggests that when used with anti-cancer drugs called PARP inhibitors, the combination is effective and does not harm normal cells,” says the study’s senior investigator, Ronit Yarden, PhD. She is an assistant professor in the department of human science at the Georgetown University School of Nursing & Health Studies and a member of Georgetown Lombardi Comprehensive Cancer Center.
Yarden and her colleagues at ARO, Israel and University of Turin, Italy utilize a Georgetown-developed procedure called “conditionally reprogrammed cells.” This allows cells to grow indefinitely, allowing the team to study the agents in a patient’s prostate cancer cells.
Their work has been published in Oncotarget.
Their work shows that when either MEB55 or ST362 are combined with a PARP inhibitor, the cells die. The synthetic plant hormones prevent the DNA repair process that occurs after the cell’s DNA is copied and before it divides. The PARP inhibitor shuts down a second repair pathway. This leaves cancer cells with no alternative but to die.
“Mistakes in copying DNA are especially prevalent in cancer cells, so without any way to repair their DNA, these cells self destruct,” Yarden says.
The notion to use PARP inhibitors arises from their use in ovarian and breast. There cancers develop due to mutated BRCA1/BRCA2 genes, she says. The BRCA genes, when normal, control a DNA repair pathway. However when they are mutated, they cannot repair their genes — the same effect delivered by the synthetic hormones.
Yarden is looking ahead to being able to soon test the combination of agents in animal models of varied cancers.