RESUMEN
BACKGROUND: Nerigoside (NG), a cardenolide isolated from a commonfolk medicine, Nerium oleander Linn. (Apocynaceae), has not been explored for its biological effects. To date, cardenolides have received considerable attention in pharmacology studies due to their direct effects of apoptosis-induction or growth-inhibitory against tumor in vitro and in vivo. Whether and how NG exerts anticancer effects against colorectal cancer remains to be elucidated. PURPOSE: The aim of this study was to investigate the anticancer effect of NG in human colorectal cancer cells. METHODS: To test anticancer effect, we compared potency of NG in two colorectal cancer cell lines, HT29 and SW620 by WST-1 and colony proliferation assays. And we investigated mechanism of anticancer activities by analyzing players in apoptotic and ERK/GSK3ß/ß-catenin signaling pathways in HT29 and SW620 cells treated with NG. RESULTS: In this study, we showed that NG markedly suppressed the cell viability and colony formation of colorectal cancer cells HT29 and SW620, with no significant toxic effect on non-cancer cells NCM460. Annexin V-FITC/PI and CFSE labeling results revealed that NG suppressed cell proliferation in low concentration, along with reducing expression of PCNA, while NG induced apoptosis in high concentration,. Meanwhile, NG significantly arrested cell migration by reversal of EMT and cell cycle on G2/M. Then, we found that the ERK and GSK3ß/ß-catenin signaling pathway were noticeably blocked in CRC cells after treatment with NG. According to western blot, NG upregulated the expression of p-GSK3ß/GSK3ß and decreased especially the expression of ß-catenin in nuclear. In addition, Wnt signaling and its target genes were suppressed in response to NG. Then, the Ser9 phosphorylation of GSK3ß can be reduced / raised by GÖ 6983 / LiCl, respectively. Thus, we further confirmed that the GSK3ß/ß-catenin axis is involved in NG-prevented cell proliferation. CONCLUSION: NG inhibited the growth of colorectal cancer cells by suppressing ERK/GSK3ß/ß-catenin signaling pathway. And the GSK3ß/ß-catenin axis is involved in preventing cell proliferation and migration by NG-treatment. These results suggest that NG may be used to treat colorectal cancer, with better outcome by combining with GSK3ß inhibitor to block Wnt pathway.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , beta Catenina/metabolismo , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Células HT29 , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Terapia Molecular Dirigida/métodos , Nerium/química , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , beta Catenina/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To investigate the sociopsychological basis of hypertensive disorder in pregnancy (HDP) and explore a new pathway for etiological study of HDP. METHODS: A prospective investigation was conducted in 1154 women in second trimester pregnancy and 9 factors were surveyed using Olson marital quality questionnaire (ENRIC). The discrepancy between the norms and factor scores of ENRIC was analyzed, and the scores of ENRIC were compared between normal gravidas and patients with HDP. The correlation between ENRIC scores and the severity of the condition was also evaluated. RESULTS: The score of the 1124 gravidas for marital satisfaction was significantly higher than the norm (P<0.05), but the scores for relationship with relatives and sexual life were significantly lower (P<0.05). The other 6 factors had similar scores with the norms (P>0.05). Patients with HDP had significantly lower scores for 7 factors than the normal gravidas (P<0.05), but had comparable scores for financial arrangement and sexual life (P>0.05). The severity of HDP was not found to associate with variation of the scores for the 9 factors (P>0.05). CONCLUSIONS: Marital quality is an important social and psychological basis of HDP, and this study provides some evidence for the social and psychological investigation of the etiology of HDP.