# Resveratrol: A Review on the Biological Activity and Applications
## 3 Antitumor Properties
### Glioma, Glioblastoma and Neuroblastoma  
Neuroblastoma is an aggressive type of tumor that requires a more efficient and less cytotoxic treatment. Studies indicate that the activity of RSV in neuroblastoma cells can be mediated by functionally activated p53 [43]. RSV intervenes in the proliferation, apoptosis, and cell cycle modification of neuroblastoma cells, inducing important cytotoxicity and increased apoptosis. S-phase accumulation is connected to the downregulation of p21 and up-regulation of cyclin E [44].  
During an investigation in rat gliomas, RSV exerted important glioma cell cytotoxicity and apoptosis, induced antitumor effects on the spinal cord and intracerebral gliomas, and inhibited angiogenesis in spinal cord gliomas [45]. RSV elevates cellular cytotoxicity and inhibits the proliferation of rat neuroblastoma cells by activating mitochondria-mediated intrinsic caspase-dependent pathway [36; 46].  
Human glioma cells were utilized to comprehend the molecular mechanisms of the anticancer effect of RSV. The phytocompound caused apoptosis of glioma cells, as evaluated by lactate dehydrogenase release and internucleosomal DNA fragmentation analysis. RSV activated caspase-3, which leads to cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9 [36; 47].  
RSV has the ability to suppress the growth and proliferation of glioma and improve its apoptosis through upregulating the leucine repeat immunoglobulin-like protein 1 (LRIG1) gene expression, which stimulates antiglioma growth, suggesting that LRIG1 is a new biological objective in antiglioma cell proliferation and growth [48].  
Researchers investigated autophagy induced by RSV in human glioma cells, which inhibited growth and induced cell apoptosis. Glioma cells firmly expressing green fluorescent protein (GFP) merged to LC3, engaged more GFP-LC3-labeled autophagosomes, and elevated the percentage of cells with GFP-LC3-labeled autophagosome. Also, RSV-inducedautophagy was regulated by P38 and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway [49].  
Glioblastoma multiforme (GBM) is the most destructive intracranial tumor that over-expresses the YKL-40 gene, related to the tumor stages of human primary astrocytoma and glioma cell proliferation. It was confirmed that RSV inhibits YKL-40 expression by limiting the exertion of its supporter and decreasing messenger ribonucleacic acid (mRNA) transcription and protein activity in vitro, involving the ERK1/2 pathway [50].  
Invasion and metastasis of glioblastoma-initiating cells are accountable for the evolution and recurrence of GBM. In vitro and in vivo observations suggest that RSV inhibits the adhesion, invasion, and migration of glioblastoma-initiating cells. Furthermore, it suppresses the invasion of glioblastoma-initiating cells by the inhibition of PI3K/Akt/NF-kB signal transduction and the following suppression of MMP-2 expression [51].  
Recent findings exhibited the effect of RSV for the amelioration of glioblastoma inflammatory response by reducing NOD-like receptor protein 3 (NLRP3) inflammasome activation through inhibition of the Janus tyrosine kinase 2/signal transducer and activator of the transcription 3 (JAK2/STAT3) pathway [52].