Novel c-Myc-Targeting Compound N, N-Bis (5-Ethyl-2-Hydroxybenzyl) Methylamine for Mediated c-Myc Ubiquitin-Proteasomal Degradation in Lung Cancer Cells.
Nicharat Sriratanasak,Korrakod Petsri,Apirat Laobuthee,Worawat Wattanathana,Chanida Vinayanuwattikun,Sudjit Luanpitpong,Pithi Chanvorachote +6 more
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TLDR
EMD was identified as a novel potent compound targeting oncogenic c-Myc that may offer new opportunities for lung cancer treatment and support its use in potential new approaches to treat c- myc–driven cancer.Abstract:
Aberrant c-Myc is a common feature in the majority of human cancers and has been linked to oncogenic malignancies. As a profound activator of aggressive lung cancer, targeting c-Myc would lead to the better clinical outcome. Here we develop a novel c-Myc targeted compound N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD) and present evidence demonstrating its effectiveness in targeting c-Myc for degradation in human lung carcinoma. EMD exhibited strong cytotoxicity towards various human lung cancer cell lines ae well as chemotherapeutic-resistant patient-derived lung cancer cells through apoptosis induction, in comparison to chemotherapeutic drugs. Mechanistically, EMD eliminates c-Myc in the cells and initiates caspase-dependent apoptosis cascade. Cycloheximide chase assay revealed that EMD significantly shortened c-Myc half-life by approximately two-fold. Cotreatment of EMD with proteasome inhibitor MG132 reversed its c-Myc targeting effect, suggesting the involvement of ubiquitin-mediated proteasomal degradation in the process. We further verified that EMD strongly induced the ubiquitination of c-Myc that prompted it for protein degradation. c-Myc inhibition and apoptosis induction were additionally shown in hematologic malignant K562, indicating the generality of the observed EMD effects. Altogether, we have identified EMD as a novel potent compound targeting oncogenic c-Myc, which may offer new opportunities for lung cancer treatment. SIGNIFICANCE STATEMENT Deregulation of c-Myc is frequently associated with cancer progression. This study examined the effect of a new compound EMD in targeting c-Myc in several lung cancer cell lines and drug-resistant primary lung cancer cells. EMD induced dramatic c-Myc degradation through ubiquitin-proteasomal mechanism. The promising anti-cancer and c-Myc targeted activities of EMD support its potential new approaches to treat c-Myc driven cancer.read more
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The role of ubiquitination and deubiquitination in cancer metabolism.
TL;DR: The role of ubiquitination and deubiquitination in the regulation of cancer metabolism is discussed, aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.
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The Ubiquitin System: An Emerging Therapeutic Target for Lung Cancer.
TL;DR: The ubiquitin system, present in all eukaryotes, contributes to regulating multiple types of cellular protein processes such as cell signaling, cell cycle, and receptor trafficking, and it affects the immune response.
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Molecular landscape of c-Myc signaling in prostate cancer: A roadmap to clinical translation.
Mojdeh Amini Faskhoudi,Pejman Molaei,Mehrdokht Sadrkhanloo,Sima Orouei,M. Hashemi,Saied Bokaie,Mohsen Rashidi,Maliheh Entezari,Ali Zarrabi,Kiavash Hushmandi,Sepideh Mirzaei,Mohammad Hossein Gholami +11 more
TL;DR: In this paper , the authors focused on c-Myc signaling in prostate cancer and showed that the upregulation of c-myc upregulation is associated with reduced overall survival, clinical stage, lymph node metastasis and undesirable prognosis of PC patients.
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DPEP1 promotes the proliferation of colon cancer cells via the DPEP1/MYC feedback loop regulation.
Qian Liu,Jianzhong Deng,Chunxia Yang,Wang Yue,Ying Shen,Zhang Hua,Zhixiang Ding,Cheng Zeng,Yongzhong Hou,Lu Wenbin,Lu Wenbin,Jianhua Jin,Jianhua Jin +12 more
TL;DR: In function, the MTT, EdU, Clone Formation assays and xenograft tumors assays demonstrated that DPEP1 could boost the proliferation of colon cancer cells through theDPEP1/MYC positive feedback loop in vitro and in vivo.
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