Postoperative resveratrol administration improves prognosis of rat orthotopic glioblastomas

Abstract

BackgroundAlthough our previous study revealed lumbar punctured resveratrol could remarkably prolong the survival of rats bearing orthotopic glioblastomas, it also suggested the administration did not completely suppress rapid tumour growth. These evidences led us to consider that the prognosis of tumour-bearing rats may be further improved if this treatment is used in combination with neurosurgery. Therefore, we investigated the effectiveness of the combined treatment on rat orthotopic glioblastomas.MethodsRat RG2 glioblastoma cells were inoculated into the brains of 36 rats. The rats were subjected to partial tumour removal after they showed symptoms of intracranial hypertension. There were 28 rats that survived the surgery, and these animals were randomly and equally divided into the control group without postoperative treatment and the LP group treated with 100 μl of 300 μM resveratrol via the LP route. Resveratrol was administered 24 h after tumour resection in 3-day intervals, and the animals received 7 treatments. The intracranial tumour sizes, average life span, cell apoptosis and STAT3 signalling were evaluated by multiple experimental approaches in the tumour tissues harvested from both groups.ResultsThe results showed that 5 of the 14 (35.7%) rats in the LP group remained alive over 60 days without any sign of recurrence. The remaining nine animals had a longer mean postoperative survival time (11.0 ± 2.9 days) than that of the (7.3 + 1.3 days; p < 0.05) control group. The resveratrol-treated tumour tissues showed less Ki67 labelling, widely distributed apoptotic regions, upregulated PIAS3 expression and reduced p-STAT3 nuclear translocation.ConclusionsThis study demonstrates that postoperative resveratrol administration efficiently improves the prognosis of rat advanced orthotopic glioblastoma via inhibition of growth, induction of apoptosis and inactivation of STAT3 signalling. Therefore, this therapeutic approach could be of potential practical value in the management of glioblastomas.

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

“…RES administration via lumbar puncture effectively inhibited the growth of intracranial orthotopic rat GBM and prolonged the mean survival time of tumor-bearing animals [124]. Furthermore, a wide distribution of apoptotic foci with decreased Cyclin D1 staining, as well as enhanced autophagy with upregulated autophagy-related protein LC3 and Beclin 1, was found after RES treatment in brain tumor tissue [124,125]. Lumbar puncture is even more effective than intra-arterial RES administration.…”

“…Lumbar puncture is even more effective than intra-arterial RES administration. Shu et al [125] demonstrated a 5-fold higher concentration of RES in the whole brain after lumbar puncture compared to intra-arterial external carotid artery injection. Additionally, combination therapy such as lumbar-punctured RES with neurosurgery significantly improved the prognosis of rats with advanced orthotopic GBM, prolonged the postoperative survival time, suppressed tumor growth, induced apoptosis, and inactivated STAT3 signaling [126].…”

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

“…Resveratrol blocks the growth of U-87MG glioblastoma cells and lowers the expression of human telomerase reverse transcriptase (hTERT) as well as the catalytic subunit of the telomerase and a biomarker of cell immortalization, confirming that resveratrol can be used as a therapeutic agent for GBM [95]. The postoperative administration of resveratrol results in a significant prognosis amelioration of rat-advanced orthotopic glioblastoma by reducing growth, inducting apoptosis, and suppressing STAT3 signaling [96]. In addition, resveratrol blocks epithelial-mesenchymal transition in GBM by modulating Smad signaling [97].…”

Novel Combination of Arsenic Trioxide (As2O3) Plus Resveratrol in Inducing Programmed Cell Death of Human Neuroblastoma SK-N-SH Cells

“…Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenol stilbene found in grapes and certain medicinal plants. The plant-derived polyphenolic compound, which can be extracted from grape skin, some berries and peanuts, was reported to exhibit antitumor effects both in vitro (11,12) and in vivo (13). Resveratrol produces several beneficial effects, anti-aging, anti-carcinogenic, cardioprotective, and neuroprotective effects, which have been attributed to its antioxidant, anti-inflammatory, and gene-modulating properties (14).…”

“…Resveratrol produces several beneficial effects, anti-aging, anti-carcinogenic, cardioprotective, and neuroprotective effects, which have been attributed to its antioxidant, anti-inflammatory, and gene-modulating properties (14). The chemopreventive and therapeutic potential of resveratrol has been demonstrated in various kinds of cancers including lung, breast, prostate and skin cancer as well as neuroblastoma (13,(15)(16)(17). Resveratrol has emerged as a potential anti-tumor agent because it has the ability to modulate the cascade signaling network involved in the proliferation and survival of cancer cells (18).…”