| [PMID]: | 27959410 |
| [Au] Autor: | Zou X; Qu Z; Fang Y; Shi X; Ji Y |
| [Ad] Endereço: | Engineering Research Center of Natural Antineoplastic Drugs, Ministry of Education, Harbin, Heilongjiang 150076, P.R. China. |
| [Ti] Título: | Endoplasmic reticulum stress mediates sulforaphane-induced apoptosis of HepG2 human hepatocellular carcinoma cells. |
| [So] Source: | Mol Med Rep;15(1):331-338, 2017 Jan. |
| [Is] ISSN: | 1791-3004 |
| [Cp] País de publicação: | Greece |
| [La] Idioma: | eng |
| [Ab] Resumo: | Sulforaphane (SFN) is a naturally occurring chemopreventive agent, which effectively inhibits proliferation of HepG2 human hepatocellular carcinoma cells via mitochondriamediated apoptosis. Endoplasmic reticulum stress is considered the most important cause of cell apoptosis; therefore, the present study aimed to determine whether the endoplasmic reticulum pathway was involved in SFN-induced apoptosis of HepG2 cells. An MTT assay was used to detect the inhibitory effects of SFN on HepG2 cells. Fluorescence microscopy was used to observe the morphological changes in apoptotic cells, and western blot analysis was conducted to detect the expression of binding immunoglobulin protein (Bip)/glucose-regulated protein 78 (GRP78), Xbox binding protein1 (XBP1) and BH3 interacting domain death agonist (Bid). Furthermore, flow cytometry was used to determine the apoptotic rate of HepG2 cells, and the protein expression of C/EBP homologous protein (CHOP)/growth arrest and DNA damageinducible gene 153 (GADD153) and caspase-12 in HepG2 cells. The results indicated that SFN significantly inhibited the proliferation of HepG2 cells; the half maximal inhibitory concentration values were 32.03±0.96, 20.90±1.96 and 13.87±0.44 µmol/l, following treatment with SFN for 24, 48 and 72 h, respectively. Following 48 h of SFN treatment (10, 20 and 40 µmol/l), the apoptotic rates of HepG2 cells were 31.8, 61.3 and 77.1%, respectively. Furthermore, after 48 h of exposure to SFN, the cells presented typical morphological alterations of apoptosis, as detected under fluorescence microscopy. Treatment with SFN for 48 h also significantly upregulated the protein expression levels of Bip/GRP78, XBP1, caspase12, CHOP/GADD153 and Bid in HepG2 cells. In conclusion, endoplasmic reticulum stress may be considered the most important mechanism underlying SFN-induced apoptosis in HepG2 cells. |
| [Mh] Termos MeSH primário: |
Anticarcinógenos/farmacologia
Apoptose/efeitos dos fármacos
Carcinoma Hepatocelular/tratamento farmacológico
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Isotiocianatos/farmacologia
Neoplasias Hepáticas/tratamento farmacológico
|
| [Mh] Termos MeSH secundário: |
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/patologia
Caspase 12/metabolismo
Proteínas de Choque Térmico/metabolismo
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Fator de Transcrição CHOP/metabolismo
Proteína 1 de Ligação a X-Box/metabolismo
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Anticarcinogenic Agents); 0 (BH3 Interacting Domain Death Agonist Protein); 0 (BID protein, human); 0 (DDIT3 protein, human); 0 (Heat-Shock Proteins); 0 (Isothiocyanates); 0 (X-Box Binding Protein 1); 0 (molecular chaperone GRP78); 147336-12-7 (Transcription Factor CHOP); EC 3.4.22.- (Caspase 12); GA49J4310U (sulforafan) |
| [Em] Mês de entrada: | 1703 |
| [Cu] Atualização por classe: | 170330 |
[Lr] Data última revisão:
| 170330 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161214 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.3892/mmr.2016.6016 |
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