Working in a laboratory at Rutgers University, Drs. Paul Breslin, David Foster, and Onica LeGendre discovered how a chemical component of olive oil kills human cancer cells derived from skin fibroblasts and other cells while leaving healthy cells untouched. Oleocanthal, found mostly in Tuscan olive oils, ruptures vesicles (“pouches”) within cancer cells, releasing toxic enzymes that lead to cell death.
Lead author Dr. LeGendre described the team’s experimental findings in “(-)-Oleocanthal Rapidly and Selectively Induces Cancer Cell Death Via Lysosomal Membrane Permeabilization (LMP),” published in Molecular & Cellular Oncology. The study began when the team was reading about the effects of oleocanthal on cancer cells. Logic suggested that oleocanthal may be targeting a protein in cancer cells that leads to cell death. “We needed to determine if oleocanthal was targeting that protein and causing the cells to die,” said Dr. Breslin, in a news release from Rutgers. After Dr. Breslin met Dr. Foster during a seminar, the team set off with their hypothesis in mind.
The team applied oleocanthal to a variety of cancer cell lines, some of which were human fibroblasts of skin origin. Cells died quickly (between 30 minutes to an hour), which is much quicker than the program of apoptosis (between 16 and 24 hours). Evidently, something else was at play.
After a few more experiments, Dr. LeGendre had the answer. Oleocanthal was poking holes inside of vesicles that store cell waste — otherwise known as lysosomes — and causing enzymes to spill out and kill their own host cell. “Once you open one of those things, all hell breaks loose,” said Dr. Breslin.
Interestingly, the same was not true for healthy cells. Healthy cells exposed to oleocanthal simply stopped proliferation temporarily and started to grow again after a day. The difference between the cancer cell and healthy cell response is the stability of the lysosomal membrane. Cancer cells’ lysosomal membranes are much more susceptible to puncture by lysosomotropic agents such as oleocanthal, which acts by inhibiting acid sphingomyelinase (ASM). In healthy cells, ASM stabilizes proteins necessary to lysosomal membrane integrity.
There is a long way to go before oleocanthal can be used in anti-cancer treatments. Dr. Foster indicated the next logical step is testing the chemical in live animal models with tumors.
