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A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway
Cong Peng
Central south university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7104-5490
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background: Fyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma.
Methods: We investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma.
Results: Our findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells.
Conclusion: Our study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.
Keywords
Melanoma, Chalcone derivative, Fyn, Stat3, Cell growth
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CURRENT STATUS: Published
Version 2
Posted 03 Jun, 2020
Published
On 18 Jun, 2020
No community comments so far
Editorial decision: Accept
On 08 Jun, 2020
Review #2 received
Received 05 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Review #3 received
Received 02 Jun, 2020
Reviewer #3 agreed
On 31 May, 2020
Reviewer #2 agreed
On 30 May, 2020
Reviewers invited
Invitations sent on 30 May, 2020
Reviewer #1 agreed
On 30 May, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Major revision
On 04 May, 2020
Review #2 received
Received 30 Apr, 2020
Review #4 received
Received 30 Apr, 2020
Review #1 received
Received 30 Apr, 2020
Review #3 received
Received 30 Apr, 2020
Reviewer #4 agreed
On 22 Apr, 2020
Reviewer #1 agreed
On 20 Apr, 2020
Reviewer #2 agreed
On 20 Apr, 2020
Reviewer #3 agreed
On 20 Apr, 2020
Reviewers invited
Invitations sent on 19 Apr, 2020
Editor assigned
On 17 Apr, 2020
Editor invited
On 16 Apr, 2020
Submission checks complete
On 13 Apr, 2020
First submitted
On 11 Apr, 2020
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This preprint is under consideration at Cancer Cell International. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway
Cong Peng
Central south university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7104-5490
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 03 Jun, 2020
Published
On 18 Jun, 2020
No community comments so far
Editorial decision: Accept
On 08 Jun, 2020
Review #2 received
Received 05 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Review #3 received
Received 02 Jun, 2020
Reviewer #3 agreed
On 31 May, 2020
Reviewer #2 agreed
On 30 May, 2020
Reviewers invited
Invitations sent on 30 May, 2020
Reviewer #1 agreed
On 30 May, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Major revision
On 04 May, 2020
Review #2 received
Received 30 Apr, 2020
Review #4 received
Received 30 Apr, 2020
Review #1 received
Received 30 Apr, 2020
Review #3 received
Received 30 Apr, 2020
Reviewer #4 agreed
On 22 Apr, 2020
Reviewer #1 agreed
On 20 Apr, 2020
Reviewer #2 agreed
On 20 Apr, 2020
Reviewer #3 agreed
On 20 Apr, 2020
Reviewers invited
Invitations sent on 19 Apr, 2020
Editor assigned
On 17 Apr, 2020
Editor invited
On 16 Apr, 2020
Submission checks complete
On 13 Apr, 2020
First submitted
On 11 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background: Fyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma.
Methods: We investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma.
Results: Our findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells.
Conclusion: Our study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6