The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa.

Zhao, Fei; Zhao, Jin; Song, Lei; Zhang, Ya-Qing; Guo, Zhong; Yang, Ke-Hu

Zhao, Fei; Zhao, Jin; Song, Lei; Zhang, Ya-Qing; Guo, Zhong; Yang, Ke-Hu.

Afiliación

Zhao F; School of Medicine, Northwest Minzu University, No. 1 Northwest Xin-Cun, Cheng-Guan District, Lanzhou, 730030, Gansu, People's Republic of China.
Zhao J; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, No. 199 Dong-Gang-Xi Road, Cheng-Guan District, Lanzhou, 730000, Gansu, People's Republic of China.
Song L; School of Medicine, Northwest Minzu University, No. 1 Northwest Xin-Cun, Cheng-Guan District, Lanzhou, 730030, Gansu, People's Republic of China.
Zhang YQ; School of Medicine, Northwest Minzu University, No. 1 Northwest Xin-Cun, Cheng-Guan District, Lanzhou, 730030, Gansu, People's Republic of China.
Guo Z; School of Medicine, Northwest Minzu University, No. 1 Northwest Xin-Cun, Cheng-Guan District, Lanzhou, 730030, Gansu, People's Republic of China.
Yang KH; School of Medicine, Northwest Minzu University, No. 1 Northwest Xin-Cun, Cheng-Guan District, Lanzhou, 730030, Gansu, People's Republic of China.

Apoptosis ; 22(11): 1461-1472, 2017 Nov.

Article en En | MEDLINE | ID: mdl-28894987

RESUMEN

Polysaccharides extracted from the mushroom Grifola frondosa (GFP) are a potential anticancer agent. The objective of this study was to investigate the effect of GFP and vitamin C (VC) alone and in combination on the viability of human hepatocarcinoma SMMC-7721 and HepG2 cells. Studies designed to detect cell apoptosis and autophagy were also conducted to investigate the mechanism. Results from the cell viability assay indicated that a combination of GFP (0.2 or 0.25 mg/mL) and VC (0.3 mmol/L) (GFP/VC) led to 52.73 and 53.93% reduction in cell viability of SMMC-7721 and HepG2 cells separately after 24 h. Flow cytometric analysis indicated that GFP/VC treatment induced cell cycle arrest at the G2/M phase, and apoptosis occurred in approximately 43.62 and 42.46% of the SMMC-7721 and HepG2 cells separately. Moreover, results of Hoechst33258 and monodansylcadaverine staining, and transmission electron microscopy, showed that GFP/VC induced apoptosis and autophagy in SMMC-7721 and HepG2 cells. Western blot analysis showed changes in the expression of apoptosis-related proteins [upregulation of BAX and caspase-3, downregulation of Bcl-2, and activation of poly-(ADP-ribose)-polymerase] and autophagy protein markers (upregulation of beclin-1 and microtubule-associated protein 1A/1B light chain-3). We also demonstrated that the expression of both Akt and p-Akt was enhanced, suggesting the PI3K/Akt/mTOR pathway might not be involved in this process. Our study shows that the combined application of GFP and VC induced cell apoptosis and autophagy in vitro, and might have antitumor activity in vivo.

Asunto(s)

Antineoplásicos/farmacología; Ácido Ascórbico/farmacología; Polisacáridos Fúngicos/farmacología; Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; Hepatocitos/efectos de los fármacos; Antineoplásicos/aislamiento & purificación; Apoptosis/efectos de los fármacos; Autofagia/efectos de los fármacos; Beclina-1/genética; Beclina-1/metabolismo; Caspasa 3/genética; Caspasa 3/metabolismo; Línea Celular Tumoral; Supervivencia Celular/efectos de los fármacos; Combinación de Medicamentos; Sinergismo Farmacológico; Polisacáridos Fúngicos/aislamiento & purificación; Puntos de Control de la Fase G2 del Ciclo Celular/genética; Grifola; Células Hep G2; Hepatocitos/metabolismo; Hepatocitos/patología; Humanos; Proteínas Asociadas a Microtúbulos/agonistas; Proteínas Asociadas a Microtúbulos/genética; Proteínas Asociadas a Microtúbulos/metabolismo; Poli(ADP-Ribosa) Polimerasas/genética; Poli(ADP-Ribosa) Polimerasas/metabolismo; Proteínas Proto-Oncogénicas c-akt/agonistas; Proteínas Proto-Oncogénicas c-akt/genética; Proteínas Proto-Oncogénicas c-akt/metabolismo; Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores; Proteínas Proto-Oncogénicas c-bcl-2/genética; Proteínas Proto-Oncogénicas c-bcl-2/metabolismo; Transducción de Señal; Proteína X Asociada a bcl-2/agonistas; Proteína X Asociada a bcl-2/genética; Proteína X Asociada a bcl-2/metabolismo

Palabras clave

Anticancer; Apoptosis; Autophagy; Grifola frondosa; Hepatoma; Vitamin C

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Ascórbico / Regulación Neoplásica de la Expresión Génica / Hepatocitos / Puntos de Control de la Fase G2 del Ciclo Celular / Polisacáridos Fúngicos / Antineoplásicos Idioma: En Revista: Apoptosis Año: 2017 Tipo del documento: Article Pais de publicación: Países Bajos

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