Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway In Vitro

doi:10.21873/anticanres.12073

Cited by 22 publications

(38 citation statements)

References 50 publications

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“…Suppression of MMP9 expression (by inhibiting NFκB and AP‐1) and reduction of lung metastasis by PEITC, BITC, and SFN was shown in an A549 xenograft mouse model 70. The inhibition of MMP2 activity by PEITC and BITC, which was accompanied by reduced cell migration and invasion, was also reported in the human melanoma cell line A375.S271 and in the mouse melanoma cell line B16F10 72. Both MMP2 and MMP9 are client proteins of HSP90 (Table 1), but whether or not the inhibitory effect of PEITC could be in part a consequence of HSP90 inhibition has not been investigated.…”

Section: Peitc and Epigenetic Regulation: An Emerging Fieldmentioning

confidence: 81%

Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1

Naidu

Suzuki

Yamamoto

et al. 2018

Molecular Nutrition Food Res

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Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45‐related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on‐target selectivity, which should be carefully considered in the design of future clinical trials.

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Section: Peitc and Epigenetic Regulation: An Emerging Fieldmentioning

confidence: 81%

Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1

Naidu

Suzuki

Yamamoto

et al. 2018

Molecular Nutrition Food Res

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“…Recent studies suggest that the isothiocyanates phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC), like SFN, can inhibit metastatic cell activity and migration. [35, 36] Therefore, to determine if SFN’s ability to increase the vacuolar pH is drug-specific, we checked to see if PEITC and BITC could similarly trigger an increase in vacuolar pH. If so, it would suggest that isothiocyanates in general and not SFN specifically kill cells via this mechanism.…”

Section: Resultsmentioning

confidence: 99%

Sulforaphane Alters the Acidification of the Vacuole to Trigger Cell Death

Wilcox

Murphy

Tucker

et al. 2018

Preprint

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Sulforaphane (SFN) is a compound [1-isothiocyanato-4-(methylsulfinyl)- butane] found in broccoli and other cruciferous vegetables that is currently of interest because of its potential as a chemopreventive and a chemotherapeutic drug. Recent studies in a diverse range of cellular and animal models have shown that SFN is involved in multiple intracellular signaling pathways that regulate cell death, cell cycle progression, and cell invasion. In order to better understand the mechanisms of action behind SFN-induced cell death, we undertook an unbiased genome wide screen with the yeast knockout (YKO) library to identify SFN sensitive (SFNS) mutants. Our mutants were enriched with knockouts in genes linked to vacuolar function suggesting a link between this organelle and SFN’s mechanism of action in yeast. Our subsequent work revealed that SFN increases the vacuolar pH of yeast cells and that varying the vacuolar pH can alter the sensitivity of yeast cells to the drug. In fact, several mutations that lower the vacuolar pH in yeast actually made the cells resistant to SFN (SFNR). Finally, we show that human lung cancer cells with more acidic compartments are also SFNR suggesting that SFN’s mechanism of action identified in yeast may carry over to higher eukaryotic cells.

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“…harvested and loaded onto 10% polyacrylamide gels and copolymerized with 0.2% gelatin. Gel was soaked twice in 2.5% Triton X-100 in dH 2 O at 25˚C for 30 min as previously described (28,30). Then, gel was incubated in zymogen developing buffer (Sigma Aldrich), containing 50 mM Tris (pH 7.5), 200 mM NaCl, 5 mM CaCl 2 , 1 μM ZnCl 2 and 0.02% Brij 35, overnight at 37˚C.…”

Section: Methodsmentioning

confidence: 99%

“…Band corresponding to MMP-2 activity was stained with 0.2% Coomassie blue in 10% acetic acid and 50% methanol and photographed. The band of gelatinolytic activity was measured using NIH Image J software, version 1.47 (National Institutes of Health, Bethesda, MA, USA), as previously described (30,31).…”

Section: Methodsmentioning

confidence: 99%

“…Cell migration and invasion in vitro were examined by using Collagen and Matrigel assay system as previously described (28,30). Briefly, U-2 OS cells (5×10 4 cells/well) in serum-free McCoy's 5A culture medium containing different concentrations of fisetin (0, 2.5, 5 and 10 μM) were placed in the upper chamber (transwell insert) (8 μm pore size; Millipore, Temecula, CA, USA) which was coated with 50 μl collagen (for cell migration examination) overnight.…”

Section: Cell Migration and Invasion Analyzed With The Transwell Assaymentioning

confidence: 99%

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Fisetin Suppresses Human Osteosarcoma U-2 OS Cell Migration and InvasionviaAffecting FAK, uPA and NF-ĸB Signaling PathwayIn Vitro

Chen

Peng

Lai

et al. 2019

In Vivo

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Background/Aim: Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. Materials and Methods: The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro. Results: Fisetin reduced the viability of cells at different concentrations (2.5, 5 and 10 μM) as measured by flow cytometric assay. Fisetin suppressed cell mobility, migration and invasion of U-2 OS cells, as shown by wound healing assay and transwell filter chambers, respectively. The gelatin zymography assay showed that fisetin inhibited MMP-2 activity in U-2 OS cells. Results from western blotting indicated that fisetin reduced the levels

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Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway In Vitro

Cited by 22 publications

References 50 publications

Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1

Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1

Sulforaphane Alters the Acidification of the Vacuole to Trigger Cell Death

Fisetin Suppresses Human Osteosarcoma U-2 OS Cell Migration and InvasionviaAffecting FAK, uPA and NF-ĸB Signaling PathwayIn Vitro

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