RESUMEN
D-limonene is recognized as a potential chemotherapeutic agent, however, the details of this mechanism remain unclear. In this study, we investigated the effects of d-limonene on colon cancer cell viability and its potential mechanism of action in vitro. After 48 h of treatment, d-limonene suppressed the viability of LS174T cells in a dose-dependent manner and caused a dose-dependent apoptotic cell death. D-limonene activated caspase-3 and -9 and PARP cleavage in a dose-dependent manner. Moreover, an increase in Bax protein and cytosol cytochrome c from mitochondria and a decrease in bcl-2 protein were observed following treatment with d-limonene. In addition, d-limonene decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3ß (Ser9), suggesting that d-limonene induced apoptosis via the mitochondrial death pathway and the suppression of the PI3K/Akt pathway.
Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias del Colon/patología , Ciclohexenos/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Terpenos/farmacología , Western Blotting , Caspasa 3/metabolismo , Proliferación Celular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Citocromos c/metabolismo , Citosol/efectos de los fármacos , Citosol/metabolismo , Citometría de Flujo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Limoneno , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Células Tumorales Cultivadas , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The aim was to investigate the expression of the CXCR4 protein in five molecular subtypes of breast cancer. The authors randomly selected the breast cancer paraffin-embedded specimens of the Affiliated Third Hospital of Harbin Medical University between 2007 and 2009. Details are as follows: basal-like subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6 (+), n = 36; normal breast subtype-ER (-), PR (-), C-erbB-2 (-), CK5/6(-), n = 40; luminal A subtype-ER/PR (+), C-erbB-2 (-), n = 38; luminal B subtype-ER/PR (+), C-erbB-2 (+), n = 60; C-erbB-2 (+) subtype-ER (-), PR (-), C-erbB-2 (+), n = 58. Using the immunohistochemistry method, the authors detected the expression of the CXCR4 protein in the five subtypes. The CXCR4 protein expression in the basal-like subtype was the highest, and that in the luminal A subtype was the lowest. In terms of five molecular subtypes of breast cancer, the differences in CXCR4 protein expression were significant (p < .001). In terms of C-erbB-2 expression, tumor stage, and lymph node metastasis of breast cancer, the differences in CXCR4 protein expression were significant (p < .01).