Current cancer drug targets · 2026
Anticancer Effect and Mechanism of Novel c-Myc Inhibitor BP1 on Hepatocellular Carcinoma.
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Cao Shengkun, Yang Qingqing, Xu Wangwei, Ni Qiaoyun, Lin Qisi
Аннотация
INTRODUCTION: c-Myc is a pivotal oncogenic transcription factor in hepatocellular carcinoma (HCC), driving tumor progression by regulating genes involved in proliferation, metabolism, and cell survival. Although c-Myc represents an attractive therapeutic target, the development of effective and safe small-molecule inhibitors remains challenging. The present study aimed to evaluate the anticancer activity and underlying mechanism of a newly synthesized c-Myc inhibitor, BP1, in hepatocellular carcinoma.
METHODS: BP1 was synthesized as a novel small-molecule inhibitor targeting c-Myc. Its antitumor effects were investigated in Huh7 and HepG2 hepatocellular carcinoma cell lines. Cell viability and clonogenic growth were assessed using MTT and colony formation assays, respectively. Cell migration and invasion were examined by wound-healing and Transwell assays. Apoptosis was analyzed by Annexin V/PI flow cytometry. The effects of BP1 on cMyc protein stability, downstream target gene expression, and glycolysis-related enzymes were evaluated by Western blotting and quantitative PCR. In addition, the pharmacokinetic properties of BP1 were characterized in vivo following single-dose administration using LC-MS/MS analysis and compartmental modeling.
RESULTS: BP1 treatment markedly reduced cell viability, clonogenic capacity, migration, and invasion in hepatocellular carcinoma cells, while significantly increasing apoptotic cell death. Mechanistic studies showed that BP1 decreased c-Myc protein stability without altering c-Myc mRNA levels, resulting in the suppression of c-Myc-dependent transcriptional programs and downregulation of key glycolytic enzymes. These changes were associated with impaired cellular energy metabolism. Pharmacokinetic analysis revealed rapid systemic clearance and a relatively short plasma half-life of BP1, indicating a low likelihood of drug accumulation following administration.
DISCUSSION: The present findings indicate that BP1 exerts its antitumor effects primarily through post-transcriptional destabilization of c-Myc, rather than inhibition of c-Myc gene expression. By disrupting c-Myc-driven metabolic and proliferative signaling pathways, BP1 effectively suppresses multiple malignant phenotypes of hepatocellular carcinoma cells. The observed pharmacokinetic profile further suggests that BP1 may offer advantages in terms of safety related to systemic exposure.
CONCLUSION: BP1 demonstrates potent anticancer activity against hepatocellular carcinoma cells by destabilizing c-Myc, inhibiting proliferation and motility, inducing apoptosis, and interfering with c-Myc-regulated metabolic pathways. In addition to its favorable pharmacokinetic properties, BP1 represents a promising lead compound for further preclinical development in hepatocellular carcinoma.
METHODS: BP1 was synthesized as a novel small-molecule inhibitor targeting c-Myc. Its antitumor effects were investigated in Huh7 and HepG2 hepatocellular carcinoma cell lines. Cell viability and clonogenic growth were assessed using MTT and colony formation assays, respectively. Cell migration and invasion were examined by wound-healing and Transwell assays. Apoptosis was analyzed by Annexin V/PI flow cytometry. The effects of BP1 on cMyc protein stability, downstream target gene expression, and glycolysis-related enzymes were evaluated by Western blotting and quantitative PCR. In addition, the pharmacokinetic properties of BP1 were characterized in vivo following single-dose administration using LC-MS/MS analysis and compartmental modeling.
RESULTS: BP1 treatment markedly reduced cell viability, clonogenic capacity, migration, and invasion in hepatocellular carcinoma cells, while significantly increasing apoptotic cell death. Mechanistic studies showed that BP1 decreased c-Myc protein stability without altering c-Myc mRNA levels, resulting in the suppression of c-Myc-dependent transcriptional programs and downregulation of key glycolytic enzymes. These changes were associated with impaired cellular energy metabolism. Pharmacokinetic analysis revealed rapid systemic clearance and a relatively short plasma half-life of BP1, indicating a low likelihood of drug accumulation following administration.
DISCUSSION: The present findings indicate that BP1 exerts its antitumor effects primarily through post-transcriptional destabilization of c-Myc, rather than inhibition of c-Myc gene expression. By disrupting c-Myc-driven metabolic and proliferative signaling pathways, BP1 effectively suppresses multiple malignant phenotypes of hepatocellular carcinoma cells. The observed pharmacokinetic profile further suggests that BP1 may offer advantages in terms of safety related to systemic exposure.
CONCLUSION: BP1 demonstrates potent anticancer activity against hepatocellular carcinoma cells by destabilizing c-Myc, inhibiting proliferation and motility, inducing apoptosis, and interfering with c-Myc-regulated metabolic pathways. In addition to its favorable pharmacokinetic properties, BP1 represents a promising lead compound for further preclinical development in hepatocellular carcinoma.