Isothiocyanates inhibit the invasion and migration of C6 glioma cells by blocking FAK/JNK-mediated MMP-9 expression

Lee, Changsu; Cho, Hyun-Ji; Jeong, Yun-Jeong; Shin, Jeong Cheol; Park, Kwan‐Kyu; Park, Yoon-Yub; Bae, Young‐Seuk; Chung, Il Yong; Kim, Mi‐Hyun; Kim, Cheorl-Ho; Jin, Fansi; Chang, Hyeun‐Wook; Chang, Young‐Chae

doi:10.3892/or.2015.4292

Cited by 40 publications

(35 citation statements)

References 49 publications

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“…In various types of cancers, the phosphorylation of JNK is a downstream molecule of FAK. 31, 32 We therefore sought to determine whether JNK was involved in WISP-1-induced VEGF-A expression. Pretreatment of cells with JNK siRNA inhibited JNK expression as well as WISP-1-induced VEGF-A expression (Figures 3c and d).…”

Section: Resultsmentioning

confidence: 99%

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WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

et al. 2017

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In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We demonstrate a positive correlation between WISP-1 and VEGF-A expression in human osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal kinase (JNK), and hypoxia-inducible factor (HIF)-1α signaling pathways were activated after WISP-1 stimulation, while FAK, JNK, and HIF-1α inhibitors or small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA-381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the FAK/JNK/HIF-1α signaling pathways, as well as via down-regulation of miR-381 expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.

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Section: Resultsmentioning

confidence: 99%

“…32 Isothiocyanates inhibit the migration and invasion of C6 glioma cells via the FAK/JNK pathway. 31 Thus, FAK regulates JNK activation through activation of the Tie2-FAK and Akt pathways. In this study, we found that JNK phosphorylation was reduced by FAK inhibitor.…”

Section: Discussionmentioning

confidence: 99%

WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

et al. 2017

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“…(20-28), we focused on apoptosis in order to elucidate which underlined pathways were involved in accounting for the observed reduction of viability levels in A375 cells. Overall, ITCs induced apoptosis by activating a number of initiator (8,9,4) and effector (3,6,7) caspases indicating the involvement of various apoptotic pathways including but not limited to, the extrinsic (caspase 8), intrinsic (caspase 9) and ER-dependent (caspase 4) pathways. To the best of our knowledge, this is the first report that (i) describes a novel experimental in vitro model based on the utilization of low ITC concentrations in a manner described herein and (ii) how it exerts an anticancer effect uniquely to melanoma cells (without affecting other non-melanoma and normal keratinocyte cells) by inducing apoptosis at concentrations substantially lower than those utilized in current bibliography.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies have utilized non-melanoma (8)(9)(10)(11)(12)(13)(14) and melanoma (15)(16)(17)(18)(19) experimental models based on a single bolus addition of large ITC concentrations where a wide range of biological effects were documented but without provision of appropriate control (non-tumorigenic) cells. Similarly, we have been able to document such anticancer activity in melanoma cells but also in control keratinocyte cells suggesting a non-specific potency towards any type of cell line (tumorigenic or not).…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells

Mantso

Sfakianos

Atkinson

et al. 2016

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Abstract. Background: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma. Materials and MethodsMalignant melanoma is the fifth most common cancer in UK with its incidence rates being continuously rising faster than any other malignancy (1). Epidemiological studies suggest that an increased dietary consumption of cruciferous vegetables can reduce cancer incidence. These effects can be attributed to the high levels of glucosinolates (GSLs) present which are sulphur-containing glycosides and precursors for a group of compounds called isothiocyanates (ITCs) (2). Briefly, upon mechanical disruption of the plant cell wall (e.g. by chewing), the enzyme myrosinase is released which then catalyses the hydrolysis of GSLs to ITCs, with subsequent release of HSO 4 -and D-glucose (3). Different GSLs can form different ITCs, since glucoraphanin acts as the precursor for sulforaphane (SFN), gluconasturtin for phenethyl isothiocyanate (PEITC) and glucotropaeolin for benzyl isothiocyanate (BITC) (4). There is much speculation as to how ITCs may exhibit their chemotherapeutic effects, but the likelihood is that multiple molecular events are responsible. Potential biochemical mechanisms include (i) inhibition of carcinogen activity via suppression of phase I enzymes in xenobiotic metabolism, (ii) stimulation of phase II enzymes and (iii) induction of apoptosis (5, 6). Despite many reports demonstrating ITCs' effectiveness against different cancers there have been a limited number of studies investigating their ability to induce apoptosis in human malignant melanoma cells (7) which their results are dependent on the utilization of high concentrations of ITCs. 6303

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“…1,37 SFN also inhibits the invasion and migration of C6 glioma cells by blocking FAK/JNK-mediated MMP-9 expression. 21 …”

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confidence: 99%

Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell–like spheroids, and tumor xenografts through multiple cell signaling pathways

Bijangi-Vishehsaraei

Saadatzadeh

Wang

et al. 2017

Journal of Neurosurgery

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Objective Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)—a constituent of cruciferous vegetables with a multitargeted effect—as a therapeutic agent for GBM. Methods The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. Results SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell–induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. Conclusions These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.

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Isothiocyanates inhibit the invasion and migration of C6 glioma cells by blocking FAK/JNK-mediated MMP-9 expression

Cited by 40 publications

References 49 publications

WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma

Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells

Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell–like spheroids, and tumor xenografts through multiple cell signaling pathways

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