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1.
Bioorg Chem ; 122: 105757, 2022 05.
Article in English | MEDLINE | ID: mdl-35339928

ABSTRACT

The incidence and number of deaths caused by melanoma have been increasing in recent years, and the pigment C-phycocyanin (C-PC) appears as a possible alternative to treat this disease. So, the objective of this study was to combine in silico and in vitro analysis to understand the main anti-melanoma pathways exerted by C-PC. We evaluated the ability of C-PC to bind to the main cellular targets related in the progression of melanoma through molecular docking, and the reflection of this bind in the biological effects in the B16F10 cell line through in vitro analysis. Our results showed that C-PC was able to bind BRAF and MEK, which are related to the signal transduction pathway for proliferation and survival. There was also an interaction between C-PC and cyclin-dependent kinase 4 and 6. In vitro analysis demonstrated that C-PC decreased B16F10 cell proliferation, as observed by cell viability and mitotic index assays. C-PC also interacted with matrix metalloproteinase 2 and 9 and N-cadherin, which may have caused the decrease in cell migration observed in vitro. Besides that, C-PC interacts with VEGF, a factor responsible for regulating the proliferation and cellular invasion pathways. Finally, C-PC did not alter the cell viability of the non-tumoral melanocytes. Therefore, C-PC is a strong anti-tumor candidate for the treatment of melanoma, since it acts in different cellular pathways of melanoma, without causing damage to non-tumoral cells.


Subject(s)
Melanoma , Phycocyanin , Cell Line, Tumor , Cell Proliferation , Humans , Matrix Metalloproteinase 2 , Melanoma/drug therapy , Molecular Docking Simulation , Phycocyanin/pharmacology
2.
Cell Biol Int ; 43(2): 214-219, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30597722

ABSTRACT

Chemotherapy may be followed by multiple drug resistance (MDR). This is an obstacle in the treatment of cancer. It is therefore essential to understand the mechanisms underlying tumor resistance, especially those involved in the cell target/MDR relationship. To investigate this, the effects of exposing cells to UVB (to target DNA), UVA, and H2 O2 (to target the cell membrane) were observed in K562 (non MDR) and FEPS (MDR) cell lines. The K562 cells were more sensitive to UVA than the FEPS cells. The FEPS cell line was more resistant to H2 O2 than K562, only presenting cytotoxicity 72 h after being exposed to 40 mM, with no ROS increase until 48 h. Both cell lines were sensitive to UVB, presenting cytotoxicity after 24 h, mainly by apoptosis, and showed an increase in ROS levels. Our results indicate that agents acting on DNA may be able to overcome the MDR phenotype.


Subject(s)
Apoptosis/drug effects , Drug Resistance, Neoplasm , Hydrogen Peroxide/pharmacology , Ultraviolet Rays , Apoptosis/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Humans , K562 Cells , Leukemia, Erythroblastic, Acute/metabolism , Leukemia, Erythroblastic, Acute/pathology , Phenotype , Reactive Oxygen Species/metabolism
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