In English

Evaluation of mitochondrial targeting antioxidants impact on malignant melanoma progression in vitro and in vivo

Julia Jonsson
Göteborg : Chalmers tekniska högskola, 2018.
[Examensarbete på avancerad nivå]

Malignant melanoma is a type of skin cancer with one of the highest increases in incidence over the past decades. In addition, melanoma is highly metastatic and the 5-year prognosis of patients suffering from inner organ metastasis is only 15 %. Melanomagenesis often occurs as a result of UV-radiation and the production of reactive oxygen species (ROS) in melanocytes. Due to the fact that cancer cells produce more ROS than normal cells, it has been believed that antioxidant treatment could prevent cancer. However, results from studies investigating antioxidant effects on cancer show that cancer progression is worsened by antioxidants. Instead it has been hypothesized that targeting ROS at their site of production could reduce malignant melanoma progression. Superoxide production, which takes place in the mitochondria, is increased in cancer cells and promotes survival and invasiveness of cancer. A potential cancer treatment could therefore be targeting this overproduction of superoxide by mitochondria-targeting antioxidants. In this project the mitochondrial antioxidants mitoQ and mitoTempo were evaluated both in vitro and in vivo in order to investigate if treatment with mitochondrial antioxidants could inhibit malignant melanoma progression. In order to do so, proliferation and invasion studies were conducted in vitro as well as an assessment of the mitochondrial antioxidants scavenging abilities. MitoTempo was administered in vivo to a transgenic mouse model of melanoma and survival was examined. Our results show that mitoQ is toxic to cells and does not act as a mitochondrial antioxidant in vitro. MitoTempo scavenges mitochondrial superoxide while increasing hydrogen peroxide and increases mitochondrial membrane potential in vitro. Additionally, mitoTempo reduces survival in vivo due to increased tumor growth. These results indicate that the prospect of using mitoQ or mitoTempo as possible drugs for the treatment of malignant melanoma does not look promising.

Nyckelord: Malignant melanoma, mitochondria, oxidative stress, ROS, antioxidants, cancer progression

Publikationen registrerades 2018-10-05.

CPL ID: 256092

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