Methylwogonin exerts anticancer effects in A375 human malignant melanoma cells through apoptosis induction, DNA damage, cell invasion inhibition and downregulation of the mTOR/PI3K/Akt signalling pathway.

Methylwogonin exerts anticancer effects in A375 human malignant melanoma cells through apoptosis induction, DNA damage, cell invasion inhibition and downregulation of the mTOR/PI3K/Akt signalling pathway.

Publication date: Jul 01, 2019

The main purpose of the present research was to study the anticancer effects of methylwogonin in A375 human malignant melanoma cells by evaluating its effects on apoptosis, DNA fragmentation, cancer cell invasion and the mTOR/PI3K/AKT signalling pathway.

Effects on cell cytotoxicity were evaluated by MTT assay while a clonogenic assay determined the effects of methylwogonin on colony formation. Fluorescence microscopy evaluated apoptotic effects of methylwogonin in these cells using acridine orange/propidium iodide and Hoechst 33342 staining dyes. Gel electrophoresis evaluated the effects of methylwogonin on DNA fragmentation while the Matrigel invasion assay evaluated the effects of the drug on cancer cell invasion. Effects of methylwogonin on the mTOR/PI3K/AKT signalling pathway were evaluated by western blot assay.

Methylwogonin induces concentration-dependent as well as time-dependent growth inhibitory effects inducing significant cytotoxicity in these cancer cells. Methylwogonin led to dose-dependent inhibition of colony formation in A375 human malignant melanoma cells. The number of cell colonies decreased significantly as the methylwogonin dose increased from 0, 50, 150, to 300 μM. Methylwogonin treatment of cells at lower doses led to yellow fluorescence (early apoptosis), which changed to red/orange fluorescence, indicating late apoptosis at higher doses. Similar results were obtained using Hoechst 33342 staining, revealing that 50, 150 and 300 μM doses of methylwogonin led to significant morphological changes including chromatin condensation, fragmented nuclei and cellular shrinkage. DNA ladder formation was also observed, and this effect increased with increasing doses of methylwogonin. Methylwogonin also inhibited cancer cell invasion in a dose-dependent manner.

Different doses of methylwogonin led to concentration-dependent downregulation of phosphorylated PI3K, AKT and mTOR.

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Chen, J., Huang, C., Liu, F., Xu, Z., Li, L., Huang, Z., and Zhang, H. Methylwogonin exerts anticancer effects in A375 human malignant melanoma cells through apoptosis induction, DNA damage, cell invasion inhibition and downregulation of the mTOR/PI3K/Akt signalling pathway. 23760. 2019 Arch Med Sci (15):4.

Concepts Keywords
AKT Phosphoinositide 3-kinase
Akt Apoptosis
Apoptosis MTOR
Apoptotic Oncology
Assay Tyrosine kinase receptors
Chromatin Cell signaling
Colony Protein kinases
Condensation Signal transduction
Cytotoxicity Branches of biology
Downregulation Enzymes
Fluorescence Apoptosis
Fluorescence Microscopy Gel electrophoresis
Fragmentation Condensation
Gel Electrophoresis Protein kinase B
Hoechst
Malignant Melanoma
Morphological
MTOR
Nuclei
Phosphorylated
PI3K
Red Orange
Sci
Signalling Pathway
Staining
Western Blot

Semantics

Type Source Name
pathway BSID Melanoma
gene UNIPROT IK
disease MESH growth
gene UNIPROT GKN2
disease DOID cancer
disease MESH cancer
disease MESH DNA fragmentation
gene UNIPROT MTOR
disease MESH DNA damage
pathway BSID Apoptosis
disease DOID malignant melanoma
disease MESH malignant melanoma

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