Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation

Kolli-Bouhafs, K.; Boukhari, Abdelaziz; Abusnina, Abdurazzag; Velot, Émilie; Gies, Jean-Pierre; Lugnier, Claire; Rondé, Philippe

doi:10.1007/s10637-011-9777-3

Cited by 85 publications

(54 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since then, increasing numbers of studies have focused on TQ in cancer therapy. Numerous in vitro and in vivo studies have investigated the antitumor activity of TQ in several types of cancer (6,14,19,(27)(28)(29)33). In tumor protein p53-null myeloblastic leukemia HL-60 cells, TQ induced apoptosis through an intrinsic signaling pathway (34).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown the antitumor and anticarcinogenic activities of TQ in numerous types of cancer, including breast cancer, glioblastoma and lymphoma (27)(28)(29). In order to elucidate the molecular mechanisms underlying the function of TQ, the effect of TQ on colon cancer cells was examined in the present study.…”

Section: Effect Of Tq On the Viability Of Colon Cancer Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

2016

View full text Add to dashboard Cite

Abstract. In the present study, the effects and molecular mechanisms of thymoquinone (TQ) on colon cancer cells were investigated. Cell viability was determined using a Cell Counting Kit-8 assay, and the results revealed that treatment with TQ significantly decreased cell viability in COLO205 and HCT116 cells in a dose-dependent manner. TQ treatment additionally sensitized COLO205 and HCT116 cells to cisplatin therapy in a concentration-dependent manner. To investigate the molecular mechanisms of TQ action, western blot analysis was used to determine the levels of phosphorylated p65 and nuclear factor-κB (NF-κB)-regulated gene products vascular endothelial growth factor (VEGF), c-Myc and B-cell lymphoma 2 (Bcl-2). The results indicated that TQ treatment significantly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TQ treatment. Treatment with TQ also decreased the expression levels of VEGF, c-Myc and Bcl-2. In addition, the inhibition of NF-κB activation with a specific inhibitor, pyrrolidine dithiocarbamate, potentiated the induction of cell death and caused a chemosensitization effect of TQ in colon cancer cells. Overall, the results of the present study suggested that TQ induced cell death and chemosensitized colon cancer cells by inhibiting NF-κB signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Tq On the Viability Of Colon Cancer Cellsmentioning

confidence: 99%

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

2016

View full text Add to dashboard Cite

show abstract

“…Indeed, FAK regulates the turnover of adhesion molecules and drives cell movement [5]. Downregulation and inhibition of FAK protein, which efficiently prevent migration of cancer cells, have been demonstrated in many in vitro and in vivo studies [23][24][25]. Phosphorylated FAK (pFAK), an active form of FAK, is also shown to be essential for an activation of cell protrusions mediated by Rac1 and Cdc42 proteins [26,27].…”

Section: Discussionmentioning

confidence: 99%

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Chaotham

Chanvorachote

2015

J Nat Med

View full text Add to dashboard Cite

Metastatic cancer cells have been shown to have aggressive behaviors accounting for the high incidence of chemotherapeutic failure and mortality. Because migration and invasion are crucial behaviors for cancer cell dissemination, promising compounds exhibiting potential antimigration effects are of interest for metastasis-based therapeutic approaches. This study aimed to evaluate the activity of a bibenzyl, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), isolated from Dendrobium ellipsophyllum Tang and Wang, in the suppression of migration in human lung cancer cells. TDB at nontoxic concentrations (1 and 5 µM) significantly inhibited the motility of lung cancer cells in scratch-wound assay. Chemotaxis-induced migration and invasion assays also revealed that the cell motility dramatically diminished in the cells treated with 1-5 µM TDB. Western blot analysis provided the underlying molecular mechanism, showing that TDB reduced such cell migration and invasion by decreasing migration-regulating proteins, including integrins αv, α4, β1, β3 and β5, as well as downstream signaling proteins, such as activated focal adhesion kinase (pFAK), activated Ras-related C3 botulinum toxin substrate 1 (Rac1-GTP) and cell division control protein 42 (Cdc42). As the presence of cellular protrusion, called filopodia, has been indicated as a hallmark of migrating cells, we showed that the reduction of the mentioned proteins correlated well with the disappearance of filopodia. In summary, this study demonstrates the promising activity of TDB and its mechanism in the inhibition of lung cancer cell migration, which might be useful for encouraging the development of this compound for antimetastatic approaches.

show abstract

“…MMPs, members of the neutral endopeptidase family that can catalyze the degradation of ECM components, are thought to play an important role in tumor invasion and metastasis in colon carcinoma and many other human cancers, and their action in tumors is inhibited by specific tissue inhibitors (TIMPs) (61,62). In our present western blot analysis results, CFZ alone or combined with CPT-11 diminished MMP1 and MMP9 protein expression, while it increased the TIMP1 protein levels in SW620 cells, which was correlated with the invasion and migration inhibition function of CFZ.…”

Section: Discussionmentioning

confidence: 99%

Enhanced anti-colorectal cancer effects of carfilzomib combined with CPT-11 via downregulation of nuclear factor-κB in vitro and in vivo

Tang

et al. 2014

International Journal of Oncology

View full text Add to dashboard Cite

Upregulation of nuclear factor-κB (NF-κB) in colorectal carcinoma (CRC) accelerates tumor growth, whereas, irinotecan (CPT-11)-induced NF-κB activation reduces chemosensitivity and weakens the anti-colorectal cancer function itself, while proteasome inhibitors can inhibit NF-κB and improve the effect of chemotherapy. Carfilzomib (CFZ) is a novel proteasome inhibitor that has been recently approved by the FDA and is in clinical use for the treatment of multiple myeloma, but little is known about its activity against CRC. The aim of the present study was to explore whether CFZ alone or in combination with CPT-11 is effective in CRC treatment. We evaluated the novel therapeutic ability and mechanism of action of CFZ in CRC in vitro and in vivo. SW620 cells were incubated with CFZ alone or in combination with CPT-11. Cell proliferation was assessed by WST-1 and clonogenic assays, the cytotoxic interaction was assessed with a combination index (CI). Cell cycle progression was analysed with flow cytometry. Cell apoptosis was evaluated by detecting the Annexin V/propidium iodide (PI) ratio, caspase 3 and CD95 expression, and with TUNEL staining. Cell migration and invasion was determined with a wound-healing assay and a Transwell matrix penetration assay. A CRC xenograft model was established to monitor tumor growth. EMSA was used to analyse NF-κB activation and western blot analysis was used to detect the protein levels of related signaling factors. CFZ significantly inhibited the growth of SW620 cells, and had synergistic inhibitory effects with CPT-11 on survival and colony formation; possibly by inhibition of NF-κB activation, MEK/ERK and PI3K/AKT pathway factor dephosphorylation and survivin downregulation. Co-administration of CFZ and CPT-11 induced G2/M arrest, increased p21WAF1/CIP, and decreased mutant p53 and cdc25c expression. Induction of apoptosis was accompanied by marked increases in PARP cleavage, caspase 3 activation, an increase of CD95 and p-p38, and ATF3 activation. Combination treatment lowered the invasive and migration ability of SW620 cells, reduced MMP and increased TIMP protein expression. Finally, co-administration of CFZ and CPT-11 suppressed tumor growth and increased apoptosis compared with single-agent treatment in SW620 xenograft models correlated with NF-κB downregulation. Carfilzomib alone or in combination with CPT-11 is effective against colorectal cancer through inhibition of multiple mechanisms related to NF-κB, and could be a potential novel therapy for CRC.

show abstract

Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation

Cited by 85 publications

References 48 publications

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Enhanced anti-colorectal cancer effects of carfilzomib combined with CPT-11 via downregulation of nuclear factor-κB in vitro and in vivo

Contact Info

Product

Resources

About