Abstract
Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. In this study, we found that pterostilbene inhibited proliferation, induced intrinsic mitochondria-mediated apoptosis and caused S phase arrest, inhibited migration and excessive invasion in glioma cells. Pretreatment with the pan-caspase-inhibitor Z-VAD-FMK attenuated the PTE-induced apoptosis of glioma cells. Moreover, PTE significantly increased the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP). Inhibition of ROS with N-acetyl-l-cysteine not only rescued PTE-induced reduction of cellular viability but also prevented glioma cell apoptosis. We also discovered ERK 1/2 and JNK signaling pathways were activated by PTE and contributed to induce glioma cell apoptosis. In addition, specific inhibitors of ERK 1/2 and JNK attenuated PTE-induced apoptosis. Besides, PTE significantly reduced tumor volume and prolonged median survival of tumor-bearing rats in vivo. In summary, the results of this study indicate that the anti-tumor effect of PTE on glioma cells may provide a new treatment option for glioma patients.
Highlights
Glioma is the most general primary and lethal intracranial malignant tumor
At least three conventional mitogen-activated protein kinases (MAPK) are expressed in mammals, including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38, and the dysregulation of MAPK is closely related to the occurrence of many human tumors[33]
The activation of JNK and p38 is related to cell apoptosis under environmental stress conditions, especially under oxidative damage, it is generally believed that the activation of ERK induced by mitogens, growth factors and cytokines will trigger survival s ignals[34]
Summary
Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. Several studies report that PTE renders its anticancer effect by inhibiting proliferation and inducing apoptosis in various types of cancers, including b reast10,11, pancreatic12,13, prostate14,15, bladder[16], gastric c arcinoma17, colorectal18,19, lung[20,21], and oral c ancer[22], as well as hepatocellular c arcinoma[23,24,25] and leukemia[26,27]. The activation of JNK and p38 is related to cell apoptosis under environmental stress conditions, especially under oxidative damage, it is generally believed that the activation of ERK induced by mitogens, growth factors and cytokines will trigger survival s ignals[34]. W akimoto[36] et al a found that pterostilbene can inhibit the proliferation of triple-negative breast cancer cells and promote their apoptosis, which may cause G 0/G1 cell cycle arrest through strong and sustained activation of the ERK pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
