Curcumol has been proved to possess antitumor effects in vivo and in vitro in several cancers. Previously, we have found that curcumol induced apoptosis in CNE-2 cells, but its underlying mechanism has not yet been studied well. Recently, our team clarified that curcumol inhibited colorectal cancer cells' growth partially through insulin-like growth factor 1 receptor (IGF-1R) pathway. Given the key importance of IGF-1R pathway in tumorigenesis, we want to explore whether curcumol effects on nasopharyngeal carcinoma (NPC) cells relates to IGF-1R and its downstream pathway inactivation. In this study, we found that curcumol inhibited IGF-1R and p-Akt expression in a dose- and time-dependent way. In addition, it also regulated their downstream GSK-3β's activity in CNE-2 cells, which further triggering alterations in the expression of cycle- and apoptosis-related molecules, and then leading to G0/G1-phase arrest and apoptosis. Moreover, curcumol's effect on CNE-2 cells was partly eliminated by IGF-1R's agonist IGF-1. In conclusion, our findings indicated that the inhibitory effect of curcumol on proliferation of NPC cells is related to the inhibition of IGF-1R and its downstream PI3K/Akt/GSK-3β pathway.
Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG-132. Expression of necroptosis inhibitor caspase-8 was decreased, and levels of necroptosis proteins receptor-interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis-related proteins caspase-3, caspase-7, and caspase-9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis-inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin-1 attenuated both osthole-induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N-acetylcysteine decreased osthole-induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy. Glioma is the most common central nervous system tumor in adults and children [1,2], and glioblastoma is the most malignant glioma ranked grade Ⅳ [3]. The average incidence of glioblastoma is 3.2/100 000 population, and the 5-year survival rate is about 6.8% [4]. Although the occurrence of glioblastoma is relatively Abbreviations DCFH-DA, 2 0 , 7 0-dichloro-hydrofluorescein diacetate;
Epigallocatechin-3-gallate (EGCG), a polyphenol present in green tea, exhibits anticancer effects in various types of cancer. A number of studies have focused on the effects of EGCG on lung cancer, but not ovarian cancer. Previous reports have implicated that EGCG suppressed ovarian cancer cell proliferation and induced apoptosis, but its potential anticancer mechanisms and signaling pathways remain unclear. Thus, it is necessary to determine the anti-ovarian cancer effects of EGCG and explore the underlying mechanisms. In the present study, EGCG exerted stronger proliferation inhibition on SKOV3 cells compared with A549 cells and induced apoptosis in SKOV3 cells, as well as upregulated PTEN expression and downregulated the expression of phosphoinositide-dependent kinase-1 (PDK1), phosphor (p)-AKT and p-mTOR. These effects were reversed by the PTEN inhibitor VO-Ohpic trihydrate. The results of the mouse xenograft experiment demonstrated that 50 mg/kg EGCG exhibited increased tumor growth inhibition compared with 5 mg/kg paclitaxel. In addition, PTEN expression was upregulated, whereas the expression levels of PDK1, p-AKT and p-mTOR were downregulated in the EGCG treatment group compared with those in untreated mice in vivo. In conclusion, the results of the present study provided a new underlying mechanism of the effect of EGCG on ovarian cancer and may lead to the development of EGCG as a candidate drug for ovarian cancer therapy.
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