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Background and purpose: Several attempts have been made to synthesize and investigate modified flavonoids to improve their potential anticancer efficacy. This study aimed to determine the in vitro antiviability, anti-migration, and anti-invasive effects of two novel hesperidin glycosides, hesperidin glucoside (HG1) and hesperidin maltoside (HG2), compared to original hesperidin and diosmin. Experimental approach: Inhibitory effects on normal (MRC5) and cancer (A549) cell viability of hesperidin glycosides were investigated by the trypan blue and MTS assays. A scratch assay determined the suppressive effects on cancer cell migration, and inhibition of cancer cell invasion was investigated through Matrigel™. The selectivity index (SI), a marker of cell toxicity, was also determined for A549 relative to MRC5 cells. Findings/Results: The cell viability trypan blue and MTS assays showed similar results of the inhibition of A549 cancer cells; HG1 and HG2 had lower IC50 than original hesperidin and diosmin. The SI of HG1 and HG2 was > 2 after 72-h culture. Investigation of cell migration showed that HG1 and HG2 inhibited the ability of gap closure in a time- and dose-dependent manner. The infiltration of the Matrigel™-coated filter by A549 cells was suppressed in the presence of HG1 and HG2. This result implied that HG1 and HG2 could inhibit cancer cell invasion. Conclusion and implication: Our results suggest the inhibition of cancer cell migration and invasion in a time- and concentration-related manner with a favorable toxic profile. Moreover, HG1 and HG2 appeared potentially better agents than the original hesperidin for future anticancer development. [ABSTRACT FROM AUTHOR]

Flavonoids are a large group of polyphenols with numerous biological effects on cancer cells. They have been shown to affect proliferation via cell cycle arrest, apoptosis and necrosis and to exert anti-oxidant, anti-inflammatory and anti-mutagenic actions. Anti-cancer effects of flavonoids, mostly in preclinical evaluations, should be translated into clinical cancer treatment research, where evidence is still scarce. Although therapies targeting primary breast tumors have markedly improved, those targeting elusive micro-metastases are less effective. In this scenario, the present review discusses the anti-tumor effects of different simple natural and synthetic flavonoids on luminal and triple-negative breast cancer, highlighting biological effects such as apoptosis, epithelial-mesenchymal transition reversion, cell migration and invasion inhibition, metalloprotease inactivation/down-regulation and anti-angiogenesis, as well as compiling in vivo treatments in experimental tumor models and some specific clinical trials. In addition, this review discusses the mechanisms underlying flavonoid anti-tumor effects. Moreover, although flavonoids may be regarded as a spectrum of promising polyphenols with multifaceted anti-tumor effects, mainly applicable to metastatic breast cancer management, some major challenges and concerns about potential flavonoid therapy in luminal and triple-negative breast cancer are also discussed.

Crocus sativus L. (saffron), was applied as a spice, food colorant and medicine since four millennia ago and has been used as a remedy for various maladies. In the last three decades, the anti-primary tumor properties of saffron and its main carotenoids, crocin and crocetin, have been well explored. Despite the fact that metastasis is the leading cause of death in cancer patients, the anti-metastatic potential of saffron and its carotenoids has been surveyed only this decade. This review aims to provide an unprecedented overview of the anti-metastatic effects of saffron, crocin and crocetin, and the mechanisms underlying these effects. Investigations on various cancers demonstrated the anti-migratory, anti-invasion, anti-angiogenic potentials of saffron and its carotenoids, as well as their effects suppressing cell-ECM adhesion and enhancing cell-cell attachment. Saffron and its carotenoids exert their impact through different mechanisms such as reduction of CD34 and suppression of Wnt/β-catenin, Ras/ERK, P38, DCLK1, EMT, matrix metalloproteinases and urokinases. Crocin displayed more effective anti-metastatic potency, in comparison with saffron extract and crocetin. The bioaccessibility/bioavailability, nontoxicity on normal cells, confirmed anti-tumor efficiency and the recent evidence on the anti-metastatic potential of saffron and its carotenoids, recommends them as a propitious multipotent dietary agent and herbal medicine. [ABSTRACT FROM AUTHOR]

Background/aim: Hepatocellular carcinoma (HCC) is a main type of liver cancer with high metastatic potential, and its incidence is steadily increasing worldwide. However, the development of new drugs for the treatment of HCC is still insufficient. This study aimed to determine the anticancer effect of NSC-38270, a natural product, on HCC., Materials and Methods: After treating HCC Huh7 cells with NSC-38270, cell growth, wound healing, migration, and invasion assays were conducted. We investigated the effects of NSC-38270 on Twist1, a crucial epithelial-mesenchymal transition (EMT)-related transcription factor. In addition, apoptosis, histone H2A.X activation, and cell morphology assays were performed in Huh7 and immortalized normal liver cells following treatment with NSC-38270., Results: NSC-38270 reduced the migration and invasion ability of Huh7 cells, accompanied by a decrease in Twist1. Furthermore, NSC-38270 induced apoptosis in Huh7 cells, whereas apoptosis was not observed in immortalized normal liver cells (THLE-2 cells and Chang liver cells)., Conclusion: NSC-38270 exhibited significant inhibitory effects on the migration and invasion of Huh7 cells by repressing Twist1. Importantly, it induced cancer cell-specific apoptotic effects. These findings suggest that NSC-38270 holds promising potential as a therapeutic candidate for cancer treatment., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract Background Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells. Methods MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting. Results AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells. Conclusions Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.

Type III secretion system (T3SS) plays a critical role in host cell invasion and pathogenesis of Salmonella. We recently identified the mycotoxin fusaric acid (FA) as a T3SS inhibitor of Salmonella. Herein, twenty-two diphenylsulfane derivatives were designed and synthesized using FA as a lead compound through scaffold hopping. Among them, SL-8 and SL-19 possessing strong anti-T3SS and anti-invasion activity were identified as T3SS inhibitors with improvement in potency as compared to FA. The inhibitory mechanisms on SPI-1 did not depend on the HilD–HilC–RtsA–HilA or PhoP-PhoQ pathway or the assembly of T3SS needle complex. Accordingly, we proposed that the inhibitory effects of SL-8 and SL-19 on SPI-1 probably influence the formation of SicA/InvF-effector complex or other related proteins. [Display omitted] • 22 diphenylsulfane derivatives were designed and synthesized as T3SSinhibitors. • SL-8 and SL-19 showed improved anti-T3SS activity over fusaric acid. • SL-8 and SL-19 might influence the formation of SicA/InvF-effector complex or other related proteins. [ABSTRACT FROM AUTHOR]

Several dietary and medicinal herbs have been shown to be effective in the treatment and prevention of cancer. Although Piper nigrum has been shown to have anti-cancer activities against various cancer cells, its anti-pancreatic cancer properties have not been reported. In the present study, P. nigrum extract (PNE) inhibited proliferation of PANC-1 human pancreatic cancer cells. Flow cytometry showed G0/G1 arrest caused by PNE in PANC-1 cells. In addition, Western blot analysis showed that PNE suppressed the protein levels of cell cycle regulators such as cyclin B1, cyclin D1, survivin, and Forkhead box M1 (FoxM1). These findings suggested that the inhibitory activity of PNE against the growth of PANC-1 cells was correlated with cell cycle arrest and repression of cell cycle regulators. Wound healing and trans-well assays showed that PNE suppressed migration and invasion of PANC-1 cells. Piperine, a major alkaloid of Piper nigrum, was identified as the main component of PNE by HPLC analysis. Piperine also attenuated the cell growth, migration, and invasion of PANC-1 cells, suggesting its contribution to the anti-pancreatic cancer effects of PNE. These results demonstrate that PNE and its major constituent, piperine, have anti-pancreatic cancer properties such as growth-inhibition, anti-migration, and anti-invasion of cancer cells. [ABSTRACT FROM AUTHOR]

Chemotherapy is a palliative treatment for unresectable patients with cholangiocarcinoma (CCA). However, drug resistance is a major cause of the failure of this treatment. Derrischalcone (DC), a novel chalcone isolated from Derris indica fruit, has been shown pharmacologically active; though, the effect of DC on CCA is unknown. The present study investigated the cytotoxic, antiproliferative, anti-migration, and anti-invasion effects and underlying mechanisms of DC on CCA KKU-M156 and KKU-100 cells. Cytotoxicity and apoptosis were evaluated by acridine orange and ethidium bromide fluorescent staining. Reactive oxygen species (ROS) was measured by dihydroethidium assay. Cell proliferation and reproductive cell death were assessed by sulforhodamine B staining and colony-forming assay. Migration and invasion were determined by wound healing and transwell chamber assays. Protein expressions associated with cell death, proliferation, migration, and invasion were analyzed by western immunoblotting. We found that DC induced cytotoxicity and apoptosis in association with ROS formation and oxidative stress. Treatment with N-acetylcysteine suppressed ROS formation and attenuated DC-induced cytotoxic and apoptotic effects. DC increased the expression of p53, p21, Bax, and cytochrome c proteins in association with cell death. DC-induced antiproliferation, colony formation, anti-migration, and anti-invasion were associated with the suppression of Akt/mTOR/cyclin D1 and FAK signaling pathways. These findings suggest that the multi-targeting strategies with DC may be a novel treatment for cancer therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] NHE5, an isoform of the Na+/H+ exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143 , which has NHE5-selective inhibitory activity, using a structure–activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells. Methods: MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting. Results: AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells. Conclusions: Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound. [ABSTRACT FROM AUTHOR]

Background/Aim: KT2 is a lysine/tryptophan-rich peptide modified from Crocodylus siamensis Leucrocin I. In this study, we examined the cell toxicity, cellular uptake, anti-migration and anti-invasion activities of KT2 in A375.S2 human melanoma cells. Materials and Methods: A375.S2 cells were treated with KT2 peptide and then we performed MTT assay, study of cellular uptake by a confocal microscope, wound healing assay, transwell migration/invasion assay, and evaluation of the expression of metastasis-associated proteins. Results: KT2 can be internalized through the plasma membrane and can slightly alter cell morphology, decrease the percentage of viable cells and inhibit cell migration and invasion of A375.S2 cells in a dose-dependent manner. This peptide suppressed MMP-2 activity, as measured by gelatine zymography assay. The protein level of MMP-2 was decreased by KT2. KT2 also down-regulated metastasis pathway-related molecules, including FAK, RhoA, ROCK1, GRB2, SOS-1, p-JNK, p-c-Jun, PI3K, p-AKT (Thr308), p-AKT (Ser473), p-p38, MMP-9, NF-kB, and uPA. Conclusion: These results indicate that KT2 inhibits the migration and invasion of human melanoma cells by decreasing MMP-2 and MMP-9 expression through inhibition of FAK, uPA, MAPK, PI3K/AKT NF-kB, and RhoA–ROCK signalling pathways. These findings suggest that KT2 deserves further investigation as an anti-metastatic agent for human melanoma. [ABSTRACT FROM AUTHOR]

Background: Clerodendrum inerme is a folk medicinal plant used in the treatment of various illnesses such as a cough, scrofulous infection, venereal infection, skin diseases and tumors. It exhibited many pharmacological effects including hepatoprotective, anti-inflammatory, anti- bacterial, anti-oxidant and anticancer properties. Objective: The purpose of this study was to investigate the influence of methanolic extract of C. inerme leaves on migration, invasion and adhesion activities on human lung adenocarcinoma. Materials and methods: Cytotoxicity, cell motility, migration, invasion and adhesion abilities were detected by MTT, wound healing, trans-well mobilization, modified Boyden chamber and cell adhesion assay, respectively. Results: The results demonstrated that up to 400 µg/mL methanolic leaves extract has low toxicity on A549 cells showing more than 50% cell viability. At non-cytotoxic and sub-toxic doses (200 and 400 µg/mL) of methanolic leave extract significantly suppressed cell motility, migration, invasion and cell adhesion compared with the untreated control. Conclusion: These results suggested that methanolic leaves extract of C. inerme inhibited migration, invasion and adhesion of A549 cells. These findings showed new therapeutic potential for C. inerme in anti-metastatic therapy. [ABSTRACT FROM AUTHOR]

The therapeutics having ability to target cancer cells specifically and exhibit nominal cytopathic effect on normal healthy cells are highly significant for cancer therapeutic applications. Recombinant porcine natural killer lysin (rpNK-lysin) has proven cationic anti-bacterial and anti-tumor peptide. Herein, we report its anti-invasion and anti-metastasis effects on hepatocellular carcinoma (HCC) cells in vitro. We first investigate the maximum non-toxic concentration (MNTC) of rpNK-lysin for the normal hepato cells (L-02). Using MNTC rpNK-lysin, we explore anti-proliferative, anti-adhesive, anti-invasive and anti-metastatic effect of rpNK-lysin on three different HCC cells lines (SMMC-7721, 97-H and HepG2) through MTT, wound-healing, adhesion and invasion assay along with mRNA and protein expression. The results reveal that rpNK-lysin has potential to specifically inhibit HCC cells growth in a dose and time-dependent manner with a little cytopathic effect on the L-02 cells, effectively reduce migration, adhesion and invasion ability of HCC cells. rpNK-lysin significantly reduce Fascin1 expression, which subsequently decrease β-catenin expression and metaloproteinases (MMP-2 and MMP9). This study suggest that MNTC rpNK-lysin has an anti-invasion and anti-metastasis effect on HCC cells in vitro through inhibition of Fascin 1 expression which regulates Wnt/β-catenin signaling pathway by inducing β-catenin degradation and subsequently results in suppression of MMP-2 and MMP9 expression. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common cancers in men. Cell invasion is an important step in the process of cancer metastasis. Herein, gold nanorods (GNRs) and polyethylene glycol (PEG)-coated GNRs were conjugated with polydopamine (PDA). The PDA-nanoconjugates demonstrated excellent colloidal stability upon lyophilization and dispersion in cell culture media with or without the addition of fetal bovine albumin (FBS), compared to unconjugated GNRs. PDA-nanoconjugates exhibited a considerable cytotoxicity against DU-145 and PC3 prostate cancer cell lines over a concentration range of 48 μg/mL–12 μg/mL, while they were biocompatible over a concentration range of 3.0 μg/mL–0.185 μg/mL. Furthermore, PDA-nanoconjugates demonstrated possible anti-invasion activity towards prostate cancer cell lines, particularly DU-145 cell line, by reducing cell migration and cell adhesion properties. The PDA-nanoconjugates could be considered a promising nano-platform toward cancer treatment by reducing the invasion activity; it could also be considered a drug delivery system for chemotherapeutic agents.

Abstract Ethnopharmacological relevance Strobilanthes crispus (L.) Blume, locally known in Malaysia as " Pecah kaca " or " Jin batu ", has been traditionally used for treatment of various ailments including cancer. We previously demonstrated that a standardized bioactive subfraction of S. crispus, termed as F3, possessed potent anticancer effects in both in vitro and in vivo breast cancer models. Aim of the study To investigate the potential of F3 from S. crispus to prevent metastasis in breast cancer. Materials and methods The antimetastatic effects of F3 were first investigated on murine 4T1 and human MDA-MB-231 breast cancer cell (BCC) lines using cell proliferation, wound healing and invasion assays. A 4T1-induced mouse mammary carcinoma model was then used to determine the expression of metastasis tumor markers, epithelial (E)-cadherin, matrix metalloproteinase (MMP)-9, mucin (MUC)-1, nonepithelial (N)-cadherin, Twist, vascular endothelial growth factor (VEGF) and vimentin, using immunohistochemistry, following oral treatment with F3 for 30 days. Results Significant growth arrest was observed with F3 IC 50 values of 84.27 µg/ml (24 h) and 74.41 µg/ml (48 h) for MDA-MB-231, and 87.35 µg/ml (24 h) and 78.75 µg/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 μg/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 µg/ml, p = 0.016) and MDA-MB-231 (50 µg/ml, p = 0.040) cells compared to the untreated cultures. F3 treatment resulted in reduced tumor growth compared to untreated mice (p < 0.01) or mice treated with tamoxifen (p < 0.05). Statistical parameters (absolute count , proportion, intensity and overall scores) indicating upregulation of E-cadherin expression were statistically significant in F3-treated compared to the untreated tumor-bearing mice. Similarly, F3 significantly reduced the expression of MMP-9, MUC1, N-cadherin, Twist, VEGF and vimentin in comparison with the TM (p < 0.01) group Conclusions Our findings suggest that F3 exerts anti-metastatic effects independent of its cytotoxic effects, and these are supported by the increased expression of E-cadherin concurrent with downregulation of MMP-9, MUC1, N-cadherin, Twist, VEGF and vimentin expression in breast cancer. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Toxoplasma gondii is the causative agent of toxoplasmosis and causes serious public health problems. However, the current treatment drugs have many limitations, such as serious side effects. Niclosamide is a salicylanilide drug commonly used to treat worm infections. Herein, the effectiveness of niclosamide for the treatment of T. gondii infection was demonstrated. This study was to evaluate the in vitro and in vivo activities of niclosamide against T. gondii and to explore its mechanism of action. The in vitro cytotoxicity of niclosamide on human foreskin fibroblast cells was evaluated by MTT test. Niclosamide displayed low host toxicity and its 50% inhibitory concentration was 8.3 μg/mL. The in vitro anti-proliferation and anti-invasion effects of niclosamide on T. gondii were determined by quantitative PCR and Giemsa staining. Niclosamide also inhibited T. gondii tachyzoite proliferation, with a 50% effective concentration of 45.3 ng/mL, and reduced the invasion of cells by tachyzoites (17.8% for the parasite control versus 1.9% for the niclosamide group treated with 100 ng/mL). A model was established by infecting BALB/c mice with the virulent RH strain of T. gondii and used to determine the in vivo effects of niclosamide on acute infection. The mice infected with tachyzoites and treated with 160, 200 or 240 mg/kg·bw niclosamide for 7 days exhibited 20%, 40% and 50% survival, respectively. In addition, niclosamide reduced the parasite burden in the blood and tissues of acutely infected mice, and niclosamide induced decreases in the mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP) levels in extracellular tachyzoites, as assessed by laser confocal microscopy and a multilabel reader. These findings indicated that the mechanism of action of niclosamide might be associated with T. gondii mitochondria oxidative phosphorylation. In conclusion, our results support the efficacy of niclosamide as a potential compound for the treatment of T. gondii infection. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Ginsenoside Rg3, a naturally occurring phytochemical, serves an important role in the prevention and treatment of cancer. In the present study, with the aim to reveal the molecular mechanism of Rg3 in liver cancer cell metastasis, the anti-migration and anti-invasion effects of Rg3 on liver cancer cells were investigated. It was demonstrated that Rg3 caused marked inhibition of cell migration and invasion of human liver cancer cells, HepG2 and MHCC-97L, in vitro, and the growth of HepG2 and MHCC-97L tumors in BABL/c nude mice. The protein expression of Rho GTPase activating protein 9 (ARHGAP9) was increased both in HepG2 and MHCC-97L cells. Following ARHGAP9 knockdown, the results of Transwell and tumorigenesis assays revealed that the anti-migration, anti-invasion and anti-tumor growth effects of Rg3 were impaired significantly. The increased expression of ARHGAP9 protein induced by Rg3 was remarkably suppressed. All results suggested that ARHGAP9 protein may be a vital regulator in the anti-metastatic role of Rg3. To the best of our knowledge, the present study is the first to report that Rg3 effectively suppressed the migration and invasion of liver cancer cells by upregulating the protein expression of ARHGAP9, indicating a novel natural therapeutic agent and a therapeutic target for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5.

Background and Purpose: Several attempts have been made to synthesize and investigate modified flavonoids to improve their potential anticancer efficacy. This study aimed to determine the in vitro anti-viability, anti-migration, and anti-invasive effects of two novel hesperidin glycosides, hesperidin glucoside (HG1) and hesperidin maltoside (HG2), compared to original hesperidin and diosmin., Experimental Approach: Inhibitory effects on normal (MRC5) and cancer (A549) cell viability of hesperidin glycosides were investigated by the trypan blue and MTS assays. A scratch assay determined the suppressive effects on cancer cell migration, and inhibition of cancer cell invasion was investigated through Matrigel™. The selectivity index (SI), a marker of cell toxicity, was also determined for A549 relative to MRC5 cells., Findings/results: The cell viability trypan blue and MTS assays showed similar results of the inhibition of A549 cancer cells; HG1 and HG2 had lower IC 50 than original hesperidin and diosmin. The SI of HG1 and HG2 was > 2 after 72-h culture. Investigation of cell migration showed that HG1 and HG2 inhibited the ability of gap closure in a time- and dose-dependent manner. The infiltration of the Matrigel™-coated filter by A549 cells was suppressed in the presence of HG1 and HG2. This result implied that HG1 and HG2 could inhibit cancer cell invasion., Conclusion and Implication: Our results suggest the inhibition of cancer cell migration and invasion in a time- and concentration-related manner with a favorable toxic profile. Moreover, HG 1 and HG 2 appeared potentially better agents than the original hesperidin for future anticancer development., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2023 Research in Pharmaceutical Sciences.)

Background: The worsening problems of antibiotic resistance prompt the need for alternative strategies. Baicalin, which is isolated from Scutellaria baicalensisi, has been demonstrated to exhibit anti-inflammatory, anti-virulence and antimicrobial effects. Salmonella typhimurium is an important foodborne pathogenic bacteriaum that causes gastrointestinal disease in humans and many animals.Purpose: The aim of this study was to investigate the effects of baicalin on S. typhimurium infection in mice and its possible mechanism in vitro.Study Design: To evaluate the effect of baicalin in vivo, mice were orally administered of baicalin, and then were infected by an intragastric administration of S. typhimurium. The minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of baicalin, baicalein, and oroxylin A against S. typhimurium were detected under the guides of the Clinical and Laboratory Standards Institute. In vitro, Caco-2 cells were infected with S. typhimurium in the presence or absence of baicalin, baicalein, and oroxylin A at sub-MICs.Methods: In the in vivo experiment, the body weight loss, the serum levels of TNFα,  IL-6, and lactic dehydrogenase (LDH), the pathological changes of the caecum and the caecum bacterial burdens were examined. The MICs and MBCs of baicalin, baicalein, and oroxylin A against S. typhimurium were detected by two-fold serial dilutions. In vitro, Caco-2 cells were infected with S. typhimurium, and the invasion capacity, TNFα, nitrate, and LDH were analysed. The transcription levels of Salmonella pathogenicity island 1 virulence associated genes (sopB, sopE, sopE2) of S. typhimurium in the presence of baicalin, baicalein, and oroxylin A were detected by qRT-PCR.Results: Our results showed that baicalin significantly decreased the body weight loss, the serum levels of TNFα,  IL-6, and LDH, and the caecum bacterial burdens of mice challenged with S. typhimurium. Histological examination showed that baicalin decreased the lesion in the caecum of S. typhimurium-infected mice. MICs and MBCs of baicalin, and oroxylin A. against S. typhimurium were > 128 µg/ml. MICs and MBCs of baicalein against S. typhimurium were 64 µg/ml, and > 128 µg/ml, respectively. Pretreatment of Caco-2 cells or S. typhimurium with baicalin, baicalein, and oroxylin A significantly inhibited the invasion of Caco-2 cells by S. typhimurium in a dose-dependent manner. Sub-MICs of baicalin, baicalein, and oroxylin A also significantly decreased the levels of TNFα, nitrate, and LDH from S. typhimurium-infected Caco-2 cells. Moreover, the transcription levels of sopB, sopE, and sopE2 were significantly suppressed by baicalin, baicalein, and oroxylin A.Conclusions: These results demonstrated that baicalin is a promising agent for the prevention of S. typhimurium infection via the modulation of both bacterial virulence and host response. [ABSTRACT FROM AUTHOR]

The widespread use of plants as accessible anticancer agents leads to the identification of many natural source chemotherapeutic agents. Scutellaria one of the popular genus of flowering plants has been used for various human illnesses for thousands of years. Scutellaria has anti-metastatic, anti-proliferative, anti-invasion, anti-angiogenic and apoptosis effects in vitro as well as in vivo . Despite numerous reports on the cytotoxic-antitumor activity of the plant, there are still some issues need further consideration. Issues such as unjustified interpretations, lack of attention to the pharmacokinetics profile and weak study design may affect the final decision about the use of plants as anticancer agents and possibly needs reconsideration. In this review, we have summarized the potential health benefits of Scutellaria and its active components also the underlying mechanism of cytotoxicity and antitumor activity. Meanwhile we have discussed concerns may interfere with the precise conclusion. [ABSTRACT FROM AUTHOR]

Crocus sativus L. (saffron) has been used as a spice and as a medicine for the past four thousand years. Recently, saffron has been well documented to possess anticancer effects on primary tumors. However studies of its antimetastatic potential are lacking. The present study is a comparative investigation of the antimetastatic effects of saffron carotenoids, crocin and crocetin, on triple negative metastatic breast cancer cells (4T1) and their effects on the Wnt/β-catenin pathway. It was found that treatment of 4T1 cells with crocin and crocetin resulted in the inhibition of viability in a dose-dependent manner. Scratch and Transwell chamber assays showed that the nontoxic doses of crocin and crocetin significantly inhibited migration, cell mobility, and invasion, also attenuating adhesion to extracellular matrix. Crocin downregulated mRNA expression of FZD7, NEDD9, VIM, and VEGF-α genes and upregulated E-CAD. Crocin and crocetin exhibited comparable anti-invasion properties on 4T1 cells. However, crocin and crocetin exerted more pronounced antimigration and antiadhesion potency, respectively. Furthermore, we showed that the antimetastatic effects of crocin can occur through interfering with the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Sixty-seven (67) lactic acid bacteria (LAB) isolates belonging to Lactobacillus genus were isolated from human feces and tested for their auto-aggregation and cell surface hydrophobicity in order to establish their adhesion capabilities, a prerequisite for probiotic selection. Strains with the upmost auto-aggregation and cell surface hydrophobicity scores were identified by MALDI-TOF spectrometry and 16S rDNA sequencing as Lactobacillus plantarum (p25lb1 and p98lb1) and Lactobacillus salivarius (p85lb1 and p104lb1). These strains were also able to adhere to human epithelial colorectal adenocarcinoma Caco-2 cells, with percentages ranging from 4.68 to 9.59%. They displayed good survival under conditions mimicking the gastrointestinal environment and remarkably impeded adhesion and invasion of human Caco-2 by Listeria monocytogenes and Enteropathogenic Escherichia coli. It should also be noted that Lb. plantarum p98lb1 was able to reduce in vitro cholesterol concentration by about 32%, offering an additional health attribute. [ABSTRACT FROM AUTHOR]

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEI UT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery., (© 2023 Wiley-VCH GmbH.)

Coriolus versicolor (CV) has been used in traditional Chinese medicine for over 2000 years as a premium medicine for enhancing good health and longevity. The immunomodulatory and anti-cancer effects of polysaccharopeptides (PSP) from cultured CV have been extensively studied; however, the effect and the mechanism of action of other small molecules from CV remain unknown. Aim of the study : we aim to examine the immunomodulatory and anti-cancer effects of the small molecules from CV (SMCV) and identify the active compounds that are responsible for the biological effects against glioblastoma multiforme cells. The effects of SMCV/active compound on cytokine and MMP mRNA expressions and productions were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. An active compound from SMCV was identified with a bioassay-guided fractionation scheme. The potential mode of action of the active compound was further investigated by identifying the cell signaling pathway. The protein expressions of phospho-ERK, phospho-JNK and phospho-p38 MAPKs were measured by Western Blotting. The anti-invasive effect of SMCV/bioactive compound against T98G, lung carcinoma (A549), and breast adenocarcinoma (MDA-MB-231) cells were determined using invasion assay. Our results showed that SMCV had strong immunomodulatory effect by suppressing LPS-induced TNF-α production, whereas increasing poly I:C-induced IFN-β level in PBMac. SMCV not only possessed indirect anti-cancer effect by suppressing TNF-α-induced MMP-3 production in glioblastoma T98G cells, but also directly reduced the invasion ability of malignant cells including T98G, A549 and MDA-MB-231. Using bioassay-guided fractionation scheme, we isolated 9-KODE methyl ester (compound AM) that was responsible for the bioactivity of SMCV. This compound suppressed TNF-α-induced MMP-3 production in T98G cells and the suppression may be correlated with the inactivation of p38 mitogen-activated protein kinase (MAPK) pathway. Moreover, compound AM also directly reduced T98G cell invasion. Results of our present study provides scientific evidence that SMCV possesses immunomodulatory and anti-cancer effects. Its bioactive compound, compound AM, is a potential new drug candidate against the invasion and metastasis of glioblastoma cells. [Display omitted] • SMCV suppresses proinflammatory cytokine production but enhances anti-cancer IFN-β level. • SMCV directly inhibits glioma cell invasion, or indirectly inhibits TNF-α-induced MMP-3 production via inactivating p38 MAPK pathway. • Compound AM possesses anti-invasive effect against glioblastoma. [ABSTRACT FROM AUTHOR]

Makgeolli is a Korean traditional alcoholic beverage prepared by fermenting rice starch using nuruk. It is known for its health benefits, but the mechanisms underlying its inhibitory effects on cancer remain unclear. Here a 70% ethanol extract of Makgeolli suldeot (70EMS) was tested for its inhibitory activities against cancer metastasis. This extract interrupted the formation of the neovasculature and reduced the migratory and invasive activity of breast cancer cells. Furthermore, it dose-dependently suppressed the activity of matrix metalloproteinase (MMP)-9 and phosphorylation of ERK1/2, JNK, and Akt. Moreover, 70EMS strongly inhibited the translocation of nuclear factor-kappa B (NF-κB) into the nucleus and expression of activator protein-1 (AP-1). These data indicate that the anti-invasive effect of 70EMS may be related to the inhibition of ERK1/2, phosphorylation of JNK, and reduced expression of NF-κB and AP-1, thereby attenuating MMP-9 in human breast cancer cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Combination treatment with platycodin D and osthole. [•] The platycodin D–osthole combination inhibits proliferation and invasiveness of mammary carcinoma cells. [•] The platycodin D–osthole combination exhibits perturbations in TGF-β/Smads signaling pathway. [Copyright &y& Elsevier]

Abstract: APN inhibitors have been considered as potential anticancer agents for years. LB-4b is the first synthetic APN inhibitor to be evaluated for both of its anti-invasion and anti-angiogenesis effects. As a potent synthetic APN inhibitor (IC50 =850nM, versus bestatin of 8.1μM), LB-4b was determined to have more significant block effects to cancer cell invasion and angiogenesis than bestatin. Besides, it is able to be easily synthesized with a high total yield, while the reported synthetic methods of bestatin are much more complex. [Copyright &y& Elsevier]

Interferon-induced transmembrane protein 1 (IFITM1) has recently been identified as a new molecular marker in human colorectal cancer. However, its role in glioma carcinogenesis is not known. In this study, we demonstrated that suppression of IFITM1 expression significantly inhibited proliferation of glioma cells in a time-dependent manner. The growth inhibitory effect was mediated by cell cycle arrest. Furthermore, IFITM1 knockdown significantly inhibited migration and invasion of glioma cells, which could be attributed to decreased expression and enzymatic activity of matrix metalloproteinase 9. Taken together, these results suggest that IFITM1 is a potential therapeutic target for gliomas. [ABSTRACT FROM AUTHOR]

Abstract: Prostrate cancer constitutes the second leading cause of cancer deaths in men in United States. In the process of discovery of new antiproliferative and anti-metastatic agents against prostate cancer, marine-derived phenylmethylene hydantoin (PMH) derivatives were identified with activity level range between 50 and 200μM. 3D-QSAR CoMFA model was used in virtual screening of commercially available derivatives of PMH. PMH derivatives with manifold increase in anti-migratory and anti-invasive activities were discovered using wound-healing and Cultrex invasion assays. Benzene ring replacement with other heterocyclic rings did not significantly improve the methylene hydantoins activities. Multivariate analysis performed on the whole series of methylene hydantoins, which further supported the findings of CoMFA model. Predictive QSAR model with conventional r 2 and cross-validated coefficient (q 2) values up to 0.982 and 0.803 were established. The molecular volume (MV) and the log P were identified as critical parameters for methylene hydatoins migration inhibitory activity. PMH is a novel anti-metastatic lead class with potential therapeutic activity against prostate cancer. [ABSTRACT FROM AUTHOR]

The Ganoderma lucidum (Leyss. ex Fr.) Karst, an edible mushroom, has been utilized for centuries in East Asia to prevent or treat various diseases and to reduce the likelihood of cancer invasion and metastasis. The primary bioactive compounds are commonly considered to be polysaccharides and triterpenoids. Evidence that G. lucidum extract and its bioactive compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. This review assembles and summarizes past publications on the in vitro and in vivo effects of G. lucidum on cancer invasion and metastasis, and concludes that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2), phosphatidylinositol 3-kinase (PI 3-kinase) or Akt kinase (protein kinase B). Activation of these kinases subsequently inhibits the activity or expression of activator protein-1(AP-1) and nuclear factor-kappa B (NF-κB), resulting in the down-regulation of urokinase plaminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, interleukin (IL)-8, inducible nitric oxide (NO) and β1-integrin as shown in various cell lines or animal models. G. lucidum may be an effective nutraceutical used in the prevention of cancer metastasis. To further elucidate the bioactive components present in G. lucidum and the anti-metastatic mechanisms underlying these compounds, more in vitro and in vivo tests as well as clinical trials are necessary. [ABSTRACT FROM AUTHOR]

Abstract: YC-1 has recently been demonstrated to have potent anti-invasion and anti-metastatic activity in several cancer models, in addition to its anti-proliferation activity. However, the mechanism underlying its anti-invasion/anti-metastatic activity is largely unknown. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer in Southeast Asia. Here, we demonstrated that YC-1 inhibited invasiveness and proliferation of NPC cells, with the latter being accompanied by PARP cleavage, S-phase arrest and activation of Chk1/Chk2. We aimed at identifying novel anti-invasion mechanisms of YC-1 in NPC by a functional proteomic platform, the reverse phase protein array (RPPA). Our study revealed for the first time that multiple invasion-related signaling proteins (β-catenin, caveolin, Src and EGFR), as well as several growth-related proteins (AMPKα, phospho-acetyl-CoA carboxylase (p-ACC), HER-2 and mTOR), which were previously un-described signaling proteins altered by YC-1, were found to be down-modulated by YC-1 in NPC cells. We hypothesized that YC-1-mediated downregulation of these invasion proteins contributed to its anti-invasion activity in NPC cells. Overexpression of EGFR, activated Src or caveolin, but not β-catenin reversed the inhibitory effects of YC-1 on NPC cell invasion, with EGFR and activated Src having additional effects on rescuing NPC cells from YC-1-mediated growth inhibition. In summary, we have identified several novel anti-invasion mechanisms of YC-1 that could impact NPC, and possibly other cancers as well. [Copyright &y& Elsevier]

Abstract: Despite the demonstrated constitutive activation of NF-κB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-κB, DHMEQ (which mainly blocks nuclear translocation of activated NF-κB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G2/M cell cycle arrest and apoptosis, and downregulation of NF-κB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-κB targeting in NPC implicates the importance of targeting this pathway in NPC. [Copyright &y& Elsevier]

The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line. [ABSTRACT FROM AUTHOR]

Abstract: Principal rotenoids (deguelin, tephrosin, rotenone, and 12a-hydroxyrotenone) (3–30μM) isolated from the stems of Erycibe expansa significantly inhibited invasion of human fibrosarcoma HT1080 cells through Matrigel-coated filters and release of proMMPs-2 and 9. In addition, deguelin and tephrosin showed differentiation-inducing activity in human promyelocytic leukemia HL-60 cells. Furthermore, effects of various constituents isolated from the ethyl acetate-soluble fraction on proliferation of human leukemia U937 cells were examined. As a result, most of isoflavones and several flavans as well as rotenoids showed moderate or substantial anti-proliferative activities. [Copyright &y& Elsevier]

Prostate cancer is one of the most common cancers in men. Cell invasion is an important step in the process of cancer metastasis. Herein, gold nanorods (GNRs) and polyethylene glycol (PEG)-coated GNRs were conjugated with polydopamine (PDA). The PDA-nanoconjugates demonstrated excellent colloidal stability upon lyophilization and dispersion in cell culture media with or without the addition of fetal bovine albumin (FBS), compared to unconjugated GNRs. PDA-nanoconjugates exhibited a considerable cytotoxicity against DU-145 and PC3 prostate cancer cell lines over a concentration range of 48 μg/mL–12 μg/mL, while they were biocompatible over a concentration range of 3.0 μg/mL–0.185 μg/mL. Furthermore, PDA-nanoconjugates demonstrated possible anti-invasion activity towards prostate cancer cell lines, particularly DU-145 cell line, by reducing cell migration and cell adhesion properties. The PDA-nanoconjugates could be considered a promising nano-platform toward cancer treatment by reducing the invasion activity; it could also be considered a drug delivery system for chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

We previously reported that Momordin Ic, a natural triterpenoid saponin from the fruit of Kochia scoparia (L.) Schrad., exerts good anti-invasive activity on liver cancer partly by altering E-cadherin, VCAM-1, ICAM-1 and MMP-9. The JNK and p38-MAPK pathways differentially altered the four molecules to some extent. However, MMP-9, which is greatly suppressed by Momordin Ic, was affected by neither p38-MAPK nor JNK. Therefore, we further investigated how other signals previously found to regulate cell growth, such as COX-2 and PPARγ, function in the process of cell invasion by western blot. The results demonstrated that COX-2 and PPARγ play a significant role in Momordin Ic-inhibited cell invasion. However, COX-2 only regulated E-cadherin and ICAM-1. PPARγ was not involved in VCAM-1alteration but was significant for the expressions of other proteins. Akt, a kinase upstream of COX-2 and PPARγ, did not influence ICAM-1 but directly mediated the expression of E-cadherin, VCAM-1 and MMP-9. Momordin Ic weakens HepG2 cell invasion through PPARγ activation and COX-2 inhibition. These findings provide evidence for the anti-invasion mechanism of Momordin Ic. • COX-2 and PPARγ play a significant role in Momordin Ic-inhibited cell invasion. • COX-2 only regulated E-cadherin and ICAM-1. • Neither COX-2 nor PPARγ affected VCAM-1 level. • MMP-9,which was hardly altered by MAPK pathways was obviously the target of AKT, COX-2 and PPARγ pathway. [ABSTRACT FROM AUTHOR]

Thymoquinone (TQ) loaded monodispersed mesoporous silica nanoparticles (TQ-MSNPs) with size of 188 ± 3 nm were prepared and characterized using DLS, TEM and FTIR. These TQ-MSNPs overcome the limitations of free TQ like hydrophobicity, low aqueous and photo stability and thus enhance its anticancer activity. In vitro release kinetics showed biphasic drug release where up to 50% was released in first 8 h and subsequently 98% released after 48 h. Enhanced cytotoxicity of TQ-MSNPs was observed against MCF-7 and HeLa cell lines as compared to free TQ. DAPI and Annexin V-FITC/PI staining confirmed the induction of apoptosis in cancer cells following treatment with TQ-MSNPs. Also, TQ-MSNPs exhibited enhanced anti-invasion properties against both cell lines as very low concentration of loaded TQ imparts similar benefits as free TQ. Both TQ and TQ-MSNPs exerted their cytotoxicity via reactive oxygen species (ROS) generation, as addition of an antioxidant NAC attenuated their killing activity. Unlabelled Image • Thymoquinone has been successfully loaded within mesoporous silica nanoparticles (TQ-MSNPs). • Encapsulation enhanced its anticancer activity evaluated against MCF-7 and HeLa cell lines. • In vitro release kinetics showed biphasic release pattern of TQ with complete release at the end of 48 h. • Staining with DAPI, AnnexinV-FITC/PI and transwell invasion assay showed apoptotic and anti-invasion activity of TQ-MSNPs. • TQ-MSNPs exhibited ROS mediated apoptosis in cancer cells as addition of NAC hamper the cytotoxicity and ROS production. [ABSTRACT FROM AUTHOR]

Background/aim: KT2 is a lysine/tryptophan-rich peptide modified from Crocodylus siamensis Leucrocin I. In this study, we examined the cell toxicity, cellular uptake, anti-migration and anti-invasion activities of KT2 in A375.S2 human melanoma cells., Materials and Methods: A375.S2 cells were treated with KT2 peptide and then we performed MTT assay, study of cellular uptake by a confocal microscope, wound healing assay, transwell migration/invasion assay, and evaluation of the expression of metastasis-associated proteins., Results: KT2 can be internalized through the plasma membrane and can slightly alter cell morphology, decrease the percentage of viable cells and inhibit cell migration and invasion of A375.S2 cells in a dose-dependent manner. This peptide suppressed MMP-2 activity, as measured by gelatine zymography assay. The protein level of MMP-2 was decreased by KT2. KT2 also down-regulated metastasis pathway-related molecules, including FAK, RhoA, ROCK1, GRB2, SOS-1, p-JNK, p-c-Jun, PI3K, p-AKT (Thr308), p-AKT (Ser473), p-p38, MMP-9, NF-kB, and uPA., Conclusion: These results indicate that KT2 inhibits the migration and invasion of human melanoma cells by decreasing MMP-2 and MMP-9 expression through inhibition of FAK, uPA, MAPK, PI3K/AKT NF-kB, and RhoA-ROCK signalling pathways. These findings suggest that KT2 deserves further investigation as an anti-metastatic agent for human melanoma., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Glioblastoma (GB) represents the most common and malignant form of glioma cancer. The Gold Standard in Glioblastoma is neurosurgical tumor removal and radiotherapy treatment in concomitant with temozolomide (TMZ). Unfortunately, because of tumor chemo and radio-resistance during this therapy, the patient's outcome remains very poor, with a median overall survival of about 14.6 months. Resveratrol is a natural polyphenol with a stilbene structure with chemopreventive and anticancer properties. In the present review, we evaluated data from preclinical studies conducted with resveratrol as a possible adjuvant during the standard protocol of GB. Resveratrol can reach the brain parenchyma at sub-micromolar concentrations when administrated through conventional routes. In this way, resveratrol reduces cell invasion and increases the efficacy of radiotherapy (radiosensitizer effects) and temozolomide. The molecular mechanism of the adjuvant action of resveratrol may depend upon the reduction of PI3K/AKT/NF-κB axis and downstream targets O-6-methylguanine-DNA methyltransferase (MGMT) and metalloproteinase-2 (MMP-2). It has been reported that redox signaling plays an important role in the regulation of autophagy. Resveratrol administration by External Carotid Artery (ECA) injection or by Lumbar Puncture (LP) can reach micromolar concentrations in tumor mass where it would inhibit tumor growth by STAT-3 dependent mechanisms. Preclinical evidences indicate a positive effect on the use of resveratrol as an adjuvant in anti-GB therapy. Ameliorated formulations of resveratrol with a favorable plasmatic profile for a better brain distribution and timing sequences during radio and chemotherapy could represent a critical aspect for resveratrol use as an adjuvant for a clinical evaluation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)