Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells.

Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells.

Publication date: Jul 11, 2019

Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of ailanthone in human melanoma B16 and mouse melanoma A375 cells, the cell counting kit-8 assay, colony formation assay, DNA content analysis, Hoechst 33258, and Annexin V-FITC/PI staining were used to assess cell proliferation, cell cycle distribution, and cell apoptosis, respectively. Western blotting was performed to evaluate the expression of cell cycle- and apoptosis-related proteins and regulatory molecules. The results showed that ailanthone significantly inhibited melanoma B16 and A375 cell proliferation as well as remarkably induced cell cycle arrest at the G0-G1 phase in B16 cells and the G2-M phase in A375 cells in a dose-dependent manner. Further investigation revealed that ailanthone promoted the expression of p21 and suppressed the expression of cyclin E in B16 cells or cyclin B in A375 cells through the PI3K-Akt signaling pathway. In addition, ailanthone induced B16 and A375 cell apoptosis via a caspase-dependent mechanism. Further studies showed that ailanthone remarkably downregulated Bcl-2 and upregulated Apaf-1 and Bax, and subsequently increased mitochondrial membrane permeabilization and released cytochrome c from the mitochondria in B16 cells and A375 cells. Taken together, ailanthone induces cell cycle arrest via the PI3K-Akt signaling pathway as well as cell apoptosis via the mitochondria-mediated apoptotic signaling pathway. Ailanthone may be potentially utilized as an anti-tumor agent in the management of malignant melanoma.

Liu, W., Liu, X., Pan, Z., Wang, D., Li, M., Chen, X., Zhou, L., Xu, M., Li, D., and Zheng, Q. Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells. 23683. 2019 Biomolecules (9):7.

Concepts Keywords
Akt Branches of biology
Apoptosis Cellular processes
Apoptotic Cell signaling
Assay Melanoma
Bax Signal transduction
Caspase Apoptosis
Colony Immunology
Content Analysis Programmed cell death
Cyclin B16 Melanoma
Cytochrome Akt/PKB signaling pathway
G0 Cyclin B
G1 Phase Apoptosis
Induced Cycle
M Phase
Malignant Melanoma
Melanoma
Mitochondria
Mitochondrial Membrane
P21
PI3K
Skin Cancer
Staining
Tumor
Western Blotting

Semantics

Type Source Name
gene UNIPROT CYCS
gene UNIPROT BAX
gene UNIPROT APAF1
pathway BSID PI3K-Akt signaling pathway
gene UNIPROT PCNA
gene UNIPROT CDKN1A
pathway BSID M Phase
pathway BSID G1 Phase
pathway BSID Cell Cycle
pathway BSID Cell cycle
gene UNIPROT ANXA5
gene UNIPROT KIT
disease MESH tumor
disease DOID skin cancer
disease MESH skin cancer
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma
pathway BSID Apoptosis

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