Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells
Authors: Ling Zhou
Xiaona Liu
Qiusheng Zheng
Zhaohai Pan
Defang Li
Minjing Li
Wenjing Liu
Maolei Xu
Dan Wang
Xiaoyu Chen
Journal: Biomolecules (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: A375 cells mitochondria; B16 cells; ailanthone; cell apoptosis; cell cycle arrest.
Affiliations: Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, China., School of Pharmacy, Binzhou Medical University, Yantai 264003, Shandong, China., Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, China. .

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. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.mdpi.com 2218-273X 10 4 627 htm Retraction: Liu, W., et al. Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells. Biomolecules 2019, 9, 275 by Biomolecules Editorial Office MDPI, St. Alban-Anlage 66, 4052 Basel, Switzerland Biomolecules 2020, 10(4), 627; https: doi.org 10.3390 biom10040627 Received: 7 April 2020 Accepted: 16 April 2020 Published: 17 April 2020 The Editorial Office and the authors have taken the decision to retract the published article [1]. The Western blot data shown in Figures 6a and 6c are unacceptably similar, in particular the backgrounds show identical features. The published paper [1] will therefore be marked as retracted. MDPI is a member of the Committee on Publication Ethics and takes seriously its responsibility to publish only high-quality research. We regret that this issue was not identified earlier and apologize to readers of the journal. References Liu, W.; Liu, X.; Pan, Z.; Wang, D.; Li, M.; Chen, X.; Zhou, L.; Xu, M.; Li, D.; Zheng, Q. Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells. Biomolecules 2019, 9, 275. ,