Abstract
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.
Highlights
Introduction10%, prognosis is often extremely poor, and its incidence and mortality are higher than any other tumor type [1]
Malignant melanoma is the most lethal type of skin cancer
The results indicated that ailanthone significantly decreased the cell viability of both B16 and A375 cells in a concentration-dependent manner, with the IC50 values of 1.83 and 5.77 μM, respectively (Figure 2a)
Summary
10%, prognosis is often extremely poor, and its incidence and mortality are higher than any other tumor type [1]. It is highly invasive, blood and lymphatic vessel metastasis can occur during the early stage of tumor formation, and is one of the most malignant tumors that seriously threaten human health [2]. Despite higher patient response rates using targeted therapy and immunotherapy, the long-term survival rate of malignant melanoma remains very low [4] and is prone to drug resistance in the later stage of Biomolecules 2019, 9, 275; doi:10.3390/biom9070275 www.mdpi.com/journal/biomolecules. A retraction notice was published on 17 April 2020 in Biomolecules 2020, 10, 627; doi:10.3390/biom10040627
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