RESUMEN
Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers. Metastasis is the major leading cause of death in patients with CRC, and many patients treated with radical surgery were diagnosed with metastasis during follow-up. However, the underlying molecular mechanisms regulating CRC metastasis are still elusive. Sterol o-acyltransferase 1 (SOAT1) is a critical participant in maintaining intracellular cholesterol balance. Here, by analyzing the clinical specimens and in vitro cell line experiments, we evaluated the clinical relevance and role of SOAT1 in regulating CRC metastasis. The results revealed that SOAT1 was overexpressed in colon cancer tissues compared to peritumor tissues at mRNA and protein levels. High intratumor SOAT1 expression correlates to lymph node metastasis and indicates poor patient disease-free survival and overall survival. The silencing of SOAT1 strongly inhibited the migration and invasion ability of CRC tumor cells. These results demonstrated that SOAT1 was upregulated in colon cancer. Upregulation of SOAT1 expression may promote CRC progression by enhancing the migration and invasion ability of CRC. Our results indicate that targeting SOAT1 activity may be applied as a promising therapeutic strategy for preventing the metastasis of CRC after radical surgical treatment.
Asunto(s)
Neoplasias Colorrectales , Esterol O-Aciltransferasa , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Humanos , Pronóstico , Esterol O-Aciltransferasa/genéticaRESUMEN
Bulbus Lilii, as a medicinal and edible plant, has anti-inflammatory, anti-oxidative and immunopotentiating pharmacological activities, which seems to be therapeutic on cancer prevention. The purpose of this study was to investigate the effects of total saponins from Lilium lancifolium (TSLL) on proliferation, apoptosis and migration of human gastric carcinoma cells lines SGC-7901 and HGC-27 and its underlying mechanism. The results showed that TSLL inhibited the proliferation of gastric carcinoma cells by suppressing the level of proliferating cell nuclear antigen (PCNA) and increased p21 level. TSLL induced cells apoptosis by up-regulating expression of pro-apoptotic protein Bax and down-regulating anti-apoptotic protein Bcl-2 expression. Meanwhile, TSLL remarkably inhibited cell migration and invasion, decreased matrix metalloproteinase-2 (MMP-2) expression and increased tissue inhibitor of metalloproteinases-1 (TIMP-1) expression. Notably, TSLL had stronger anti-cancer effect on undifferentiated HGC-27 cells than differentiated SGC-7901 cells. Accordingly, TSLL might be a promising candidate to prevent and suppress the growth of gastric carcinoma cells.
RESUMEN
The potential role of total saponins extracted from Lilium lancifolium bulbs (TSLL) on the proliferation, apoptosis, migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8, clone formation assay and EdU staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test, respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24, 48 or 72 h significantly inhibited cell growth, and its IC50values were about 229, 173 and 71 mg·L⻹, respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner. TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition, TSLL had no obvious effect on epithelial mesenchymal transition (EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation, migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless, there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer cells.
Asunto(s)
Neoplasias Pulmonares , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , SaponinasRESUMEN
Genus Lilium plants contain a variety of steroidal saponins, so far at least 82 steroidal saponins have been found in the bulbs of Lilium species, including 13 spirostanol saponins (1-13), 39 isospirostanol saponins (14-52), 7 pseudospirostanol saponins (53-59), and 23 furostanol saponins (60-82). Studies have showed that these steroidal saponins exhibit a wide range of pharmacological activities, including antitumor, antibacterial, antiinflammatory, antioxidant, antidepressant, hepatoprotective, hypoglycemic, sedative-hypnotic effect, and inhibition of cAMP phosphodiesterase and Naâº-K⺠ATP, et al. This paper has classified and summarized the 82 steroidal saponins isolated and identified from the bulbs of Lilium species and their correlative biological activities. Also, their structural characteristics and structure-activities relationship have been discussed, which could provide references for further research and application development of Lilium plants.
Asunto(s)
Lilium/química , Fitosteroles/farmacología , Saponinas/farmacologíaRESUMEN
AIM: Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix. METHODS: Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H2O2. Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 µL 400 µmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS). RESULTS: Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognition-enhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognition-enhancing action: oral administration of PGS32 (0.125 mg·kg(-1)·d(-1)) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg·kg(-1)·d(-1)) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats. CONCLUSION: PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.