A new study from The Medical School of Newcastle University is assigning guilt by association to mitochondrial function and melanoma. Melanoma skin cancer cells that display high levels of pigmentation also generate a high level of reactive oxygen species (ROS) in their mitochondria, suggesting new drug targets for treatment.
“Melanoma may be preventable by using sunscreen, but too many people still die of the disease. ” said Gerald Weissmann, MD, Editor-in-Chief of the publishing journal, FASEB Journal, in a news release. “This research shows a direct relationship between pigment production (as when our skin tans) and the production of ROS by mitochondria (and/or the sun). It’s not a very attractive relationship since it leads to cancer progression.”
According to the article, “Impact of Hyperpigmentation on Superoxide Flux and Melanoma Cell Metabolism at Mitochondrial Complex II,” the research team, composed of Drs. Sarah Jayne Boulton and Mark A. Birch-Machin, analyzed the level of ROS generation and the function of mitochondrial complex II in melanoma skin cancer cell lines characterized by different degrees of pigmentation. There was a “direct and significant correlation between increased pigmentation and complex II turnover,” wrote the authors. As a result, the cells contained high levels of ROS.
To follow up on these findings, the duo induced melanin production, or hyperpigmentation, in the light- and medium-pigmented cells by supplying L-tyrosine, an amino acid vital to melanin production. This directly caused a concurrent increase in melanoma pigmentation, complex II function, and ROS generation. Although ROS levels increased 300%, the level eventually returned to baseline with longer hyperpigmentation.
“This study reports a novel correlation between a protein involved in the bioenergy process within the human skin (i.e., Complex II) and skin pigmentation,” said Dr. Birch-Machin. “This leads to interesting possibilities of complex II playing a central role in coupling stress sensing and cellular adaptation via ROS signalling and as this study was performed in skin cancer cells may help in the development of anti-cancer drugs.”
These potential drug candidates would join a host of new treatment options under development for melanoma, including nivolumab, which was recently approved by the FDA, and panRAF inhibitors, a recently discovered class of molecules.