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YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition

3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), the hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor, suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions. Our previous studies demonstrated that YC-1 inhibited breast cancer cell proli...

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Detalles Bibliográficos
Autores principales: Cheng, Ying, Li, Wei, Liu, Ying, Cheng, Huan-Chen, Ma, Jun, Qiu, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sun Yat-sen University Cancer Center 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777523/
https://www.ncbi.nlm.nih.gov/pubmed/22507221
http://dx.doi.org/10.5732/cjc.011.10383
Descripción
Sumario:3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), the hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor, suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions. Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions. In the current study, we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells. In the in vitro experiments, we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia. Under normoxic conditions, YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G(1) phase, and these effects were possibly related to caspase 8, p21, and p27 expression. RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions, but suppressed the expression of epidermal growth factor receptor (EGFR) at the mRNA and protein levels under normoxic conditions. In vivo, YC-1 prolonged survival, increased survival rate, decreased tumor size and metastasis rate, and inhibited tissue EGFR and HIF-1α expression. However, YC-1 exerted no obvious effect on body weight. These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects. Thus, YC-1 is a promising target drug for breast cancer.