A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway
Abstract 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-06-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01336-2 |
| _version_ | 1811222821860278272 |
|---|---|
| author | Ling Tang Jing Long Keke Li Xu Zhang Xiang Chen Cong Peng |
| author_facet | Ling Tang Jing Long Keke Li Xu Zhang Xiang Chen Cong Peng |
| author_sort | Ling Tang |
| collection | DOAJ |
| description | Abstract 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 111,277 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. |
| first_indexed | 2024-04-12T08:21:10Z |
| format | Article |
| id | doaj.art-8a797112559040a198a0ed5ea6e367c4 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-12T08:21:10Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-8a797112559040a198a0ed5ea6e367c42022-12-22T03:40:34ZengBMCCancer Cell International1475-28672020-06-0120111610.1186/s12935-020-01336-2A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathwayLing Tang0Jing Long1Keke Li2Xu Zhang3Xiang Chen4Cong Peng5Department of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityAbstract 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 111,277 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.http://link.springer.com/article/10.1186/s12935-020-01336-2MelanomaChalcone derivativeFynStat3Cell growth |
| spellingShingle | Ling Tang Jing Long Keke Li Xu Zhang Xiang Chen Cong Peng A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway Cancer Cell International Melanoma Chalcone derivative Fyn Stat3 Cell growth |
| title | A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway |
| title_full | A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway |
| title_fullStr | A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway |
| title_full_unstemmed | A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway |
| title_short | A novel chalcone derivative suppresses melanoma cell growth through targeting Fyn/Stat3 pathway |
| title_sort | novel chalcone derivative suppresses melanoma cell growth through targeting fyn stat3 pathway |
| topic | Melanoma Chalcone derivative Fyn Stat3 Cell growth |
| url | http://link.springer.com/article/10.1186/s12935-020-01336-2 |
| work_keys_str_mv | AT lingtang anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT jinglong anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT kekeli anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT xuzhang anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT xiangchen anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT congpeng anovelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT lingtang novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT jinglong novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT kekeli novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT xuzhang novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT xiangchen novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway AT congpeng novelchalconederivativesuppressesmelanomacellgrowththroughtargetingfynstat3pathway |