A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-01-30

AUTHORS

Keke Li, Shuang Zhao, Jing Long, Juan Su, Lisha Wu, Juan Tao, Jianda Zhou, JiangLin Zhang, Xiang Chen, Cong Peng

ABSTRACT

BackgroundMelanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment.MethodsWe detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma.ResultsWe found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis.ConclusionsTaken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment. More... »

PAGES

36

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12935-020-1114-5

DOI

http://dx.doi.org/10.1186/s12935-020-1114-5

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32021565


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69 expression alterations
70 expression profiles
71 findings
72 formation
73 function
74 gene enrichment
75 gene expression alterations
76 gene expression profiles
77 growth
78 immunotherapy
79 increases ROS levels
80 inhibitors
81 levels
82 lines
83 low response rate
84 mechanism
85 melanoma
86 melanoma cell growth
87 melanoma cell lines
88 melanoma cell proliferation
89 melanoma cells
90 melanoma patient treatment
91 melanoma treatment
92 novel chalcone derivatives
93 novel inhibitors
94 p53
95 pathway
96 patient treatment
97 phase
98 phase arrest
99 potential therapeutic drug
100 products
101 profile
102 proliferation
103 radiotherapy
104 rate
105 remarkable characteristics
106 replication
107 resistance
108 response rate
109 sequencing
110 severe side effects
111 side effects
112 therapeutic drugs
113 therapy
114 toxicity
115 traditional chemotherapy
116 treatment
117 tumors
118 upregulation
119 vitro
120 vivo
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