Gambogic Acid Inhibits Malignant Melanoma Cell Proliferation Through Mitochondrial p66shc/ROS-p53/Bax-Mediated Apoptosis

Liang, Lili; Zhang, Zhixin

doi:10.1159/000443102

Cited by 40 publications

(30 citation statements)

References 40 publications

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“…Multiple signalling pathways have been described for GA treatment of individual cancer cell lines . Our results and literature have shown inhibitory effect of GA in malignant melanoma . However, the mechanism of antitumour effect of GA in melanoma is not completely understood.…”

supporting

confidence: 48%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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Malignant melanoma is an aggressive form of cancer which is highly resistant to chemotherapy. We have previously found that gambogic acid (GA), a kind of polyprenylated xanthone, exhibits an antitumour role in melanoma. The study was designed to investigate novel mechanisms of the antitumour effect of GA in melanoma cells and implanted nude mice. Gambogic acid significantly decreased cell viability, increased apoptosis and reduced migration and invasion in A375 cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP cells was increased by GA. The expression of miR-199a-3p was increased by GA in A375 cells and implanted tumours, and inhibition of miR-199a-3p significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity in A375 cells. miR-199a-3p mimics reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. miR-199a-3p expression was decreased in melanoma tissues and cells, as compared with their controls. miR-199a-3p possessed a potential binding site in the 3'-UTR of zinc finger E-box binding homeobox (ZEB1). ZEB1 expression was increased in melanoma tissues and cells, as compared with their controls. ZEB1 and miR-199a-3p expression was negatively correlated in melanoma tissues. The expression of ZEB1 was decreased by GA in A375 cells and implanted tumours, and up-regulation of ZEB1 significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity. Down-regulation of ZEB1 reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. We identified the important roles of miR-199a-3p and ZEB1 in melanoma and elucidated the tumour suppressor function of miR-199a-3p through inhibition of ZEB1. The results highlight the importance of miR-199a-3p-ZEB1 signalling in antitumour effect of GA in malignant melanoma and provide novel targets for the chemotherapy of melanoma.

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supporting

confidence: 48%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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“…ARF can induce ROS generation, indicating that inhibitory role of p14 ARF in melanoma cell proliferation [29,30]. Xenografts in nude mice showed that the tumor volumes in the p16…”

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confidence: 99%

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Bai

Yu²,

Long³

et al. 2016

Cell Physiol Biochem

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Objective: This study aims to investigate the effects of CDKN2A (p16^INK4A/p14^ARF) over-expression on the proliferation and migration of human melanoma A375 cells. Methods: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16^INK4A and p14^ARF groups. The expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein was detected by qRT-PCR and Western blotting. CCK-8, flow cytometry and Transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively. The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo. Results: Compared with pigmented nevi tissues, CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) mRNA and protein expression were significantly decreased in melanoma tissues. CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) over-expression inhibited proliferation, migration, invasion and progression from G0/G1 to S phase of A375 cells and xenograft tumor growth, but promoted apoptosis. Conclusion: Our study demonstrated that over-expression of CDKN2A (p16^INK4A) and CDKN2A (p14^ARF) suppressed proliferation and migration of human melanoma A375 cells.

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“…The tumor suppressor p53 plays a vital role in genome stability and p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy [12,13]. The proteins encoded by the TP53 gene bind to DNA, regulating gene expression and preventing genome mutation.…”

Section: Introductionmentioning

confidence: 99%

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer

Liu¹,

Chen

et al. 2017

Cell Physiol Biochem

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Aims: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. Methods: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. Results: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. Conclusion: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.

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Gambogic Acid Inhibits Malignant Melanoma Cell Proliferation Through Mitochondrial p66shc/ROS-p53/Bax-Mediated Apoptosis

Cited by 40 publications

References 40 publications

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer

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