Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Chemistry, Jinan University, Guangzhou (China)
- Institute of Hematology, Jinan University, Guangzhou (China)
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong (China)
- First Affiliated Hospital, Jinan University, Guangzhou (China)
Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities of cisplatin.
- OSTI ID:
- 22606198
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 477; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway
AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo
Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells
Journal Article
·
Fri Mar 09 23:00:00 EST 2012
· Experimental Cell Research
·
OSTI ID:22212312
AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo
Journal Article
·
Thu Nov 24 23:00:00 EST 2016
· Biochemical and Biophysical Research Communications
·
OSTI ID:22696704
Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells
Journal Article
·
Sat Aug 15 00:00:00 EDT 2015
· Toxicology and Applied Pharmacology
·
OSTI ID:22465802