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1,1-Bismethanes induce autophagic cell death in estrogen receptor negative breast cancer

Vanderlaag, Kathy ; Su, Yunpeng ; Frankel, Arthur E ; Burghardt, Robert C ; Barhoumi, Rola ; Chadalapaka, Gayathri ; Jutooru, Indira ; Safe, Stephen

BMC cancer, 2010-12, Vol.10, p.669 [Revista revisada por pares]

BioMed Central Ltd

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  • Título:
    1,1-Bismethanes induce autophagic cell death in estrogen receptor negative breast cancer
  • Autor: Vanderlaag, Kathy ; Su, Yunpeng ; Frankel, Arthur E ; Burghardt, Robert C ; Barhoumi, Rola ; Chadalapaka, Gayathri ; Jutooru, Indira ; Safe, Stephen
  • Materias: Autophagy (Cytology) ; Breast cancer ; Cancer ; Care and treatment ; Causes of ; Cell death ; Cell proliferation ; Chemotherapy ; Control ; Development and progression ; Health aspects ; Physiological aspects
  • Es parte de: BMC cancer, 2010-12, Vol.10, p.669
  • Descripción: A novel series of methylene-substituted DIMs (C-DIMs), namely 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes containing t-butyl (DIM-C-pPhtBu) and phenyl (DIM-C-pPhC6H5) groups inhibit proliferation of invasive estrogen receptor-negative MDA-MB-231 and MDA-MB-453 human breast cancer cell lines with IC50 values between 1-5 uM. The main purpose of this study was to investigate the pathways of C-DIM-induced cell death. The effects of the C-DIMs on apoptotic, necrotic and autophagic cell death were determined using caspase inhibitors, measurement of lactate dehydrogenase release, and several markers of autophagy including Beclin and light chain associated protein 3 expression (LC3). The C-DIM compounds did not induce apoptosis and only DIM-C-pPhCF.sub.3 exhibited necrotic effects. However, treatment of MDA-MB-231 and MDA-MB-453 cells with C-DIMs resulted in accumulation of LC3-II compared to LC3-I protein, a characteristic marker of autophagy, and transient transfection of green fluorescent protein-LC3 also revealed that treatment with C-DIMs induced a redistribution of LC3 to autophagosomes after C-DIM treatment. In addition, the autofluorescent drug monodansylcadaverine (MDC), a specific autophagolysosome marker, accumulated in vacuoles after C-DIM treatment, and western blot analysis of lysates from cells treated with C-DIMs showed that the Beclin 1/Bcl-2 protein ratio increased. The results suggest that C-DIM compounds may represent a new mechanism-based agent for treating drug-resistant ER-negative breast tumors through induction of autophagy.
  • Editor: BioMed Central Ltd
  • Idioma: Inglés
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