An Indian origin researcher along with other colleagues have indicated that the most common breast cancer uses the most efficient, powerful food delivery system known in human cells and blocking that system kills it.
This method of starving cancer cells could provide new options for patients, particularly those resistant to standard therapies such as tamoxifen, according to Georgia Health Sciences University researchers.
Human estrogen receptor-positive breast cancer cells thriving in a Petri dish or transplanted onto mice die when exposed to a drug that blocks the transporter, called SLC6A14, said Dr. Vadivel Ganapathy, Chairman of GHSU”s Department of Biochemistry and Molecular Biology.
“It basically starves the cancer cell,” Ganapathy, corresponding author of the study, said.
The transporter can carry 18 of the known 20 amino acids, fuel all cells need in some combination. Amino acids enable cells to make proteins, which they need to function and survive.
The cell type determines its amino acid needs and delivery system. Rapidly growing, dividing estrogen receptor-positive breast cancer needs nearly every amino acid so it makes the smart choice of utilizing the transporter that can deliver the biggest load, Ganapathy said.
SLC6A14 is the only transporter known to carry all 10 essential amino acids, essential because the body can’t make them so they have to be delivered via the bloodstream from food.
The transporter also takes eight of the nonessential amino acids along for the ride. And it is a fast ride. The transporter has three energy sources instead of the usual one or two, Ganapathy said.
While that may seem like a loss for healthy cells, it bolsters the cancer-fighting potential for drugs that block SLC6A14 by making it a more specific cancer target.
“Since the normal cells do not depend on this transporter, you can use a drug that selectively blocks it to target cancer cells,” said Ganapathy.
The compound they used is alpha-methyl-DL-tryptophan, already used in humans for short periods when they are getting a PET scan in certain areas of the brain.
When the researchers treated estrogen receptor-positive breast cancer cells with it or put it in the drinking water of the mice with the cells, rapid growth stopped and the cancer cells died.
The study has been published in the Journal of Biological Chemistry.