A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway
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.
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Posted 03 Jun, 2020
On 18 Jun, 2020
On 08 Jun, 2020
Received 05 Jun, 2020
Received 03 Jun, 2020
Received 02 Jun, 2020
On 31 May, 2020
On 30 May, 2020
Invitations sent on 30 May, 2020
On 30 May, 2020
On 26 May, 2020
On 25 May, 2020
On 25 May, 2020
On 04 May, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
On 22 Apr, 2020
On 20 Apr, 2020
On 20 Apr, 2020
On 20 Apr, 2020
Invitations sent on 19 Apr, 2020
On 17 Apr, 2020
On 16 Apr, 2020
On 13 Apr, 2020
On 11 Apr, 2020
A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway
Posted 03 Jun, 2020
On 18 Jun, 2020
On 08 Jun, 2020
Received 05 Jun, 2020
Received 03 Jun, 2020
Received 02 Jun, 2020
On 31 May, 2020
On 30 May, 2020
Invitations sent on 30 May, 2020
On 30 May, 2020
On 26 May, 2020
On 25 May, 2020
On 25 May, 2020
On 04 May, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
On 22 Apr, 2020
On 20 Apr, 2020
On 20 Apr, 2020
On 20 Apr, 2020
Invitations sent on 19 Apr, 2020
On 17 Apr, 2020
On 16 Apr, 2020
On 13 Apr, 2020
On 11 Apr, 2020
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