期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms23115979
关键词
melanoma; tetrahydrobiopterin; redox homeostasis; nitric oxide synthase; nitric oxide; reactive oxygen species
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2017/04352-0, 2019/27517-0]
- CAPES
- FAPESP [2017/10695-7, 2021/04260-3, 2021/12988-7]
- CNPq
Cutaneous melanoma is the most aggressive type of skin cancer, and it progresses through different stages. Reactive oxygen species modulate oncogenic signaling pathways in all stages of melanoma development. The altered concentration of tetrahydrobiopterin disrupts cellular redox homeostasis and contributes to melanoma progression.
Cutaneous melanoma emerges from the malignant transformation of melanocytes and is the most aggressive type of skin cancer. The progression can occur in different stages: radial growth phase (RGP), vertical growth phase (VGP), and metastasis. Reactive oxygen species contribute to all phases of melanomagenesis through the modulation of oncogenic signaling pathways. Tetrahydrobiopterin (BH4) is an important cofactor for NOS coupling, and an uncoupled enzyme is a source of superoxide anion (O-2(center dot-)) rather than nitric oxide (NO), altering the redox homeostasis and contributing to melanoma progression. In the present work, we showed that the BH4 amount varies between different cell lines corresponding to distinct stages of melanoma progression; however, they all presented higher O-2(center dot-) levels and lower NO levels compared to melanocytes. Our results showed increased NOS expression in melanoma cells, contributing to NOS uncoupling. BH4 supplementation of RGP cells, and the DAHP treatment of metastatic melanoma cells reduced cell growth. Finally, Western blot analysis indicated that both treatments act on the PI3K/AKT and MAPK pathways of these melanoma cells in different ways. Disruption of cellular redox homeostasis by the altered BH4 concentration can be explored as a therapeutic strategy according to the stage of melanoma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据