Src inhibition induces melanogenesis in human G361 cells

Ku, Kyung‐Eun; Choi, Nahyun; Oh, Sang Ho; Kim, Won‐Serk; Suh, Wonhee; Sung, Jong‐Hyuk

doi:10.3892/mmr.2019.9958

Cited by 7 publications

(8 citation statements)

References 34 publications

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“…These results contrast with those supporting the use of SRC inhibitors in resistance settings in line with the upregulation of members of the SRC‐family kinases (Girotti et al , 2013 ) and downstream SRC‐dependent effectors such as MCF2 and VAV1, two DBL family members identified through a genetic screen as candidate drug resistance in melanoma cells (Feddersen et al , 2019 ). SRC inhibitors were also reported to promote a differentiated state through the upregulation of Mitf expression and downstream melanocytic markers ( TYR , TRP1… ) via the MAPK and CREB pathways (Ku et al , 2019 ). This gives some hints of how SRC may participate in melanoma cell reprogramming.…”

Section: Discussionmentioning

confidence: 99%

The AhR‐SRC axis as a therapeutic vulnerability in BRAFi‐resistant melanoma

et al. 2022

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The nongenetic mechanisms required to control tumor phenotypic plasticity and shape drug-resistance remain unclear. We show here that the Aryl hydrocarbon Receptor (AhR) transcription factor directly regulates the gene expression program associated with the acquisition of resistance to BRAF inhibitor (BRAFi) in melanoma. In addition, we show in melanoma cells that canonical activation of AhR mediates the activation of the SRC pathway and promotes the acquisition of an invasive and aggressive resistant phenotype to front-line BRAFi treatment in melanoma. This nongenetic reprogramming identifies a clinically compatible approach to reverse BRAFi resistance in melanoma. Using a preclinical BRAFi-resistant PDX melanoma model, we demonstrate that SRC inhibition with dasatinib significantly re-sensitizes melanoma cells to BRAFi. Together we identify the AhR/SRC axis as a new therapeutic vulnerability to trigger resistance and warrant the introduction of SRC inhibitors during the course of the treatment in combination with front-line therapeutics to delay BRAFi resistance.

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Section: Discussionmentioning

confidence: 99%

The AhR‐SRC axis as a therapeutic vulnerability in BRAFi‐resistant melanoma

et al. 2022

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“…Thus, some inhibitors of EGFR kinase, such as erlotinib, afatinib, and osimertinib, are used for cancer treatment [ 40 – 42 ]. The chemicals of both cephakicine and N-methylliriodendronine can bind to EGFR, while cephakicine can bind to CASP3 and N-methylliriodendronine can dock SRC, indicating that those compounds can simultaneously affect the regulation of multiple pathways to suppress the caner or tumor initiations and development [ 43 , 44 ]. We also found that both homostephanoline and aknadinine can bind EGFR and HSP90AA1, the latter, as a molecular chaperon, responding to cancer cells to support folding and activating oncoproteins, including many kinases and transcription factors for cell growth and proliferating, so chemicals modulate Hsp90 activities working as a buffer for these regulators' activity.…”

Section: Discussionmentioning

confidence: 99%

Identification of Bioactive Components of Stephania epigaea Lo and Their Potential Therapeutic Targets by UPLC-MS/MS and Network Pharmacology

Mao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Stephania epigaea, an important traditional folk medicinal plant, elucidating its bioactive compound profiles and their molecular mechanisms of action on human health, would better understand its traditional therapies and guide their use in preclinical and clinical. This study aims to detect the critical therapeutic compounds, predict their targets, and explore potential therapeutic molecular mechanisms. This work first determined metabolites from roots, stems, and flowering twigs of S. epigaea by a widely targeted metabolomic analysis assay. Then, the drug likeness of the compounds and their pharmacokinetic profiles were screened by the ADMETlab server. The target proteins of active compounds were further analyzed by PPI combing with GO and KEGG cluster enrichment analysis. Finally, the interaction networks between essential compounds, targets, and disease-associated pathways were constructed, and the essential compounds binding to their possible target proteins were verified by molecular docking. Five key target proteins (EGFR, HSP90AA1, SRC, TNF, and CASP3) and twelve correlated metabolites, including aknadinine, cephakicine, homostephanoline, and N-methylliriodendronine associated with medical applications of S. epigaea, were identified, and the compounds and protein interactions were verified. The key active ingredients are mainly accumulated in the root, which indicates that the root is the main medicinal tissue. This study demonstrated that S. epigaea might exert the desired disease efficacy mainly through twelve components interacting via five essential target proteins. EGFR is the most critical one, which deserves further verification by biological studies.

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“…In melanocytes, the MC1R and c-Kit signaling pathways may be linked to c-Src signaling. In melanocytes, inhibition of Src kinase may increase melanogenesis through p38 and CREB signaling pathways [82].…”

Section: Skin Agingmentioning

confidence: 99%

Recent advances in pharmacological diversification of Src family kinase inhibitors

Negi¹,

Cheke²,

Patil³

2021

Egypt J Med Hum Genet

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Background Src kinase, a nonreceptor protein-tyrosine kinase is composed of 11 members (in human) and is involved in a wide variety of essential functions required to sustain cellular homeostasis and survival. Main body of the abstract Deregulated activity of Src family kinase is related to malignant transformation. In 2001, Food and Drug Administration approved imatinib for the treatment of chronic myeloid leukemia followed by approval of various other inhibitors from this category as effective therapeutics for cancer patients. In the past decade, Src family kinase has been investigated for the treatment of diverse pathologies in addition to cancer. In this regard, we provide a systematic evaluation of Src kinase regarding its mechanistic role in cancer and other diseases. Here we comment on preclinical and clinical success of Src kinase inhibitors in cancer followed by diabetes, hypertension, tuberculosis, and inflammation. Short conclusion Studies focusing on the diversified role of Src kinase as potential therapeutical target for the development of medicinally active agents might produce significant advances in the management of not only various types of cancer but also other diseases which are in demand for potent and safe therapeutics.

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Src inhibition induces melanogenesis in human G361 cells

Cited by 7 publications

References 34 publications

The AhR‐SRC axis as a therapeutic vulnerability in BRAFi‐resistant melanoma

The AhR‐SRC axis as a therapeutic vulnerability in BRAFi‐resistant melanoma

Identification of Bioactive Components of Stephania epigaea Lo and Their Potential Therapeutic Targets by UPLC-MS/MS and Network Pharmacology

Recent advances in pharmacological diversification of Src family kinase inhibitors

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