Capsaicin induces apoptosis by inhibiting mitochondrial respiration
Posting Date: September 9, 2002
Last Modified: November 1, 2001
Last Updated: 2002-09-09 11:17:23 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Scientists have discovered that capsaicin, the pungent constituent of hot chili peppers, and a more potent structurally related vanilloid found in the plant Euphorbia called resiniferatoxin, induce apoptosis of tumor cells by inhibiting mitochondrial respiration, in effect starving them of oxygen.
"Capsaicin can prevent cancer development in animal models and cause cancer cell death in cultured tumor cells," Dr. Reuben Lotan of the University of Texas M. D. Anderson Cancer Center in Houston told Reuters Health. "But the mechanism underpinning this effect has not been elucidated. Our study addressed the mechanism by which capsaicin induces cancer cell death."
In the September 4th issue of the Journal of the National Cancer Institute, Dr. Lotan and Dr. Numsen Hail, Jr., report that when they exposed human cutaneous squamous cell carcinoma (SCC) cells to capsaicin or resiniferatoxin for 12 hours, the majority of cells died.
The apoptotic effects appeared to be triggered by inhibition of mitochondrial respiration as evidenced by an increase in the permeability of the inner mitochondrial membrane. Exposure to either capsaicin or resiniferatoxin led to a "rapid increase in hydroperoxide generation and a decrease in oxygen consumption," the team reports.
This shows that "capsaicin and resiniferatoxin act at the level of oxygen consumption (respiration) in mitochondria and this causes cells to die," Dr. Lotan told Reuters Health.
When they exposed respiration-deficient clones of human SCC cells to capsaicin or resiniferatoxin, the cells released less hydroperoxide compared with control cells and were resistant to mitochondrial permeability and the induction of apoptosis.
The demonstrated apoptogenic and antiproliferative effects of these two compounds "warrant further studies in animal models and, if positive, also in clinical trials to assess the potential application of capsaicin or resiniferatoxin against skin cancer," Dr. Lotan said.
In a JNCI editorial, Dr. Young-Joon Surh of Seoul National University in South Korea congratulates the scientists for their elegant series of experiments demonstrating that the "oxidative stress that is stimulated by vanilloid treatment of SCC cells is primarily of mitochondrial origin and contributes to the death of these cells by apoptosis."
Dr. Surh also urges further study, particularly to see if the increased oxidative stress brought on by vanilloids may have harmful effects on nonmalignant cells. "If this is the case, the vanilloids would be metabolic poisons rather than valuable candidates for use in preventive therapy for skin cancer or other cutaneous disorders," the researcher cautions.
J Natl Cancer Inst 2002;94:1263-1265,1281-1292.