The Therapeutic Potential of Resveratrol in Gliomas

Abstract

Resveratrol (RSV) is found in most human foods especially fruits such as grapes, peanuts, strawberry, blueberry, cranberry, mulberry, lingberry, sparkleberry, bilberry and in flowers as well as leaves like butterfly orchid tree, eucalyptus, spruce, lily, gnetum and so many others. Functionally, RSV has the propensity to safeguard DNA as well as the induction of DNA repair. RSV is precipitously metabolized in the liver via phase-II detoxification enzymes leading to its principal urine excretion. RSV steered growth inhibition, induction of apoptosis and G0/G1phase cell cycle arrest in an experiment involving glioma cells. RVS can block the triggering of signal transducer and activator of transcription (STAT3) signaling of glioma cells. RSV subdues STAT3 signaling via the inhibition of SRC or Janus kinase (JAK2) induction, thereby inducing growth inhibitory and apoptotic properties. RSV explicitly blocks both COX-1 and COX-2 invitro. In the cancer inflammatory milieu, the blockade effects of RSV on NF-κB could also lead to the blockade of TNF-α resulting in inhibition of cancer advancement as well as metastasis.Individually, RSV has proven to very potent in glioma cells. It is able to down-regulate glioma angiogenesis as well as metastasis. In combination with other agents, RVS augment its potency in glioma. RVS is able to cross the blood brain barrier (BBB) via gap junctions making it very efficient central nervous system medication. RVS after oral administration peaks in the blood stream after one hour meaning it acts very fast. This review focuses on the neuropharmacological role of RVS in glioma.proven to have chemo-preventive effects on numerous human ailments like osteoporosis and gastric ulcers besides the cardioprotective effect mentioned above (27,32). STRUCTURE AND FUNCTIONS OF RESVERATROLRSV is a white powder with a feeble yellow cast. It is a stilbene with a natural polyphenol configuration analogous to diethylstilbestrol and estradiol (32,86). Its molecular formula is C 14 H 12 O 3 and it is commonly referred to as 3,5,4'thihydroxystilbene. Other unconventional terms use to describe this compound are: 3,4',5-stilbenetriol, (E)-5-(7-hydroxystyryl) resorcinol, (E)-5-(4-hydroxystyryl) benzene-1,3-diol. RSV occurs innately as both cis-and trans-isomers. The trans-isomer is often used in classic laboratory studies because its more physical available have has higher biological activity than the cis-isomer. On the other hand, the cis-isomer is unstably and not commercial accessible (32,144).Functionally, RSV has the propensity to safeguard DNA as well as the induction of DNA repair (17,89). Studies have proven that, at high dose, RSV does not only suppress cancer advancement but also inhibits the synthesis of RNA, DNA and

The Plant-Derived Compound Resveratrol in Brain Cancer: A Review

“…The authors demonstrated the inhibition of the expression of specific oncogenic microRNAs (miRs) such as miR-21, miR-19, and miR-30a-5p in glioma cells, which was consequently associated with altered expression of their targeting genes such as p53, STAT3, EGFR, COX-2, NF-κB, and the PI3K/AKT/mTOR signaling pathway. Moreover, RES suppressed tumor growth and prolonged survival of rats bearing intracranial C6 glioma [145]. Induction of S-G2/M cell cycle arrest by RES was also described in human GBM cell lines and was accompanied by an increase in levels of pCdc2(Y15), cyclin A, E, and B and a decrease of cyclin D1 [149].…”

“…It has been demonstrated that RES is a radiation sensitizer for highly radioresistant human SU-2 glioma stem cells. The synergistic effect of RES and radiation was seen in the inhibition of cell proliferation, induction of autophagy, promotion of apoptosis, prevention of DNA repair in the early stage, and induction of differentiation, both in vitro and in vivo [145].…”

“…Cell cycle arrest is an irreversible process that can result in apoptotic cell death [147]. RES was able to delay the cell cycle progression and inhibited the proliferation of rat C6 glioma cells by arresting the cell cycle at S phase at micromolar concentrations [145]. The authors demonstrated the inhibition of the expression of specific oncogenic microRNAs (miRs) such as miR-21, miR-19, and miR-30a-5p in glioma cells, which was consequently associated with altered expression of their targeting genes such as p53, STAT3, EGFR, COX-2, NF-κB, and the PI3K/AKT/mTOR signaling pathway.…”

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

“…Resveratrol (3,4′,5-trihydroxy-trans-stilbene) anti-cancer effects include anti-proliferation, cell cycle arrestment, and apoptosis promotion through multiple signaling pathways such as EGFR, p53, P13K/AKT/mTOR, STAT3, NF-κB, and oncogenic miRNAs [ 296 , 297 ]. Resveratrol suppresses tumor growth and prolongs survival in rats bearing intracranial C6 glioma [ 296 , 298 , 299 ]. Wang and coworkers showed a longer mean survival in C6-xenograft rats treated with resveratrol (29.75 ± 9.27 days) than the control group (15.8 ± 0.93 days) [ 296 ].…”

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

“…The RG7388/RT combination is also included in a phase I/IIa trial in patients with newly diagnosed GB without O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation (N²M² (NOA-20), NCT03158389). Nutraceutical resveratrol, which has been reported to induce p53 and its downstream targets, acted as a radiosensitizing anticancer agent for highly radioresistant human SU-2 GSC both in vitro and in vivo ( 143 , 144 ).…”