Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells

Rao, Chinthalapally V.

doi:10.1158/1940-6207.capr-13-0242

Cited by 28 publications

(23 citation statements)

References 26 publications

(49 reference statements)

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“…Moreover, we found that BITC promoted c‐Jun/AP‐1 transcriptional activation, which was responsible for miR‐99a expression in BC. Since a previous review reported antitumor effects of BITC in vitro as well as in vivo, deciphering the mechanism involved in BITC antitumor activity improved its application in cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Benzyl isothiocyanate promotes miR‐99a expression through ERK/AP‐1‐dependent pathway in bladder cancer cells

Tsai

Chen

Lin

et al. 2019

Environmental Toxicology

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Benzyl isothiocyanate (BITC), a bioactive natural product present in cruciferous vegetables, has been proved to prevent cancer progression through various mechanisms.In our previous report, we proved that BITC exhibits antitumor effects in bladder cancer by suppressing IGF1R, FGFR3, and mTOR, which is mediated by miR-99a expression. In this study, we identified the signal pathway involved in regulating miR-99a expression after BITC exposure in bladder cancer. Treatment with different BITC concentrations resulted in induction of miR-99a expression in bladder cancer cell lines. Activation of extracellular signal-regulated protein kinase (ERK) and c-jun Nterminal kinase was observed in bladder cancer after BITC treatment for 24 hours.Interestingly, by using a chemical inhibitor of candidate pathways, we found that only the ERK signal pathway is required for miR-99a expression. Furthermore, we evaluated the transcription factor that may contribute to miR-99a expression in response to BITC treatment. The results indicated that c-Jun/AP-1 was activated after BITC treatment. Moreover, we confirmed c-Jun/AP-1 activation through immunofluorescence and the luciferase reporter assay. The results showed that BITC treatment markedly improved nuclear translocation of c-Jun/AP-1 and luciferase activity dose dependently. Finally, pretreatment with the ERK inhibitor U0126 diminished c-Jun phosphorylation and transcriptional activation, suggesting that BITC elicits ERK/c-Jun signal transduction, which is responsible for miR-99a expression in bladder cancer. The present work identifies the mechanism involved in upregulation miR-99a after BITC treatment, which provides an explanation for BITC biological function in our previous work. K E Y W O R D SAP-1, BITC, bladder cancer, ERK, miR-99a

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Section: Discussionmentioning

confidence: 99%

Benzyl isothiocyanate promotes miR‐99a expression through ERK/AP‐1‐dependent pathway in bladder cancer cells

Tsai

Chen

Lin

et al. 2019

Environmental Toxicology

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“…The biological effects of isothiocyanates have long been the subject of investigation because of their potential in crop protection and human health (Brown & Morra, 1995;Vig et al, 2009;Rao, 2013). Biocidal effects on a broad range of organisms including bacteria, fungi, invertebrates, plants and vertebrates suggest that fundamental biological processes are affected.…”

Section: Discussionmentioning

confidence: 99%

“…Biocidal effects on a broad range of organisms including bacteria, fungi, invertebrates, plants and vertebrates suggest that fundamental biological processes are affected. Research into anti-cancer properties of isothiocyanates, including BITC, have identified cellular activities including interaction with detoxifying enzymes, cell-cycle arrest and associated gene activity, microtubules and mitosis, and apoptosis (Rao, 2013). Although nematicidal properties are of primary interest (Lazzeri et al, 1993;Buskov et al, 2002;Wu et al, 2011;Aissani et al, 2013), the effects of sub-lethal doses of isothiocyanates, including behaviour, locomotion and hatching (Yu et al, 2005;Zasada et al, 2009;Masler et al, 2010;Schroeder & MacGuidwin, 2010) indicate that more detailed and basic investigation of isothiocyanate interactions with nematode biological processes should add considerable value to isothiocyanates as plant-parasitic nematode control agents.…”

Section: Discussionmentioning

confidence: 99%

Benzyl isothiocyanate affects development, hatching and reproduction of the soybean cyst nematode Heterodera glycines

Masler²,

Rogers³

et al. 2014

Nematol

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Benzyl isothiocyanate (BITC), prepared in 1% methanol and applied at micro-molar doses, decreased Heterodera glycines infective second-stage juvenile (J2) movement, hatching and reproduction on soybean. Glycine max. Direct exposure of J2 to 30 ßM BITC caused an immediate decrease (17%) in J2 movement relative to 1% methanol controls, and within 3 h exposure eliminated >99% of movement. Continuous exposure of H. glycines eggs to 30 ßU or 60 /xM BITC significantly decreased percentage hatch of J2 measured at 7 days (30 ßU, 15.8 ± 2.4%; 60 ßU, 7.9 ± 2.2%) relative to controls (44.9 ± 4.1%). Control percentage hatch increased between days 7 and 14 (87.5 ± 2.3%), whereas there was no significant increase in hatch after Day 7 in either treatment group. The effect of BITC on hatch was rapid and persistent. Following 4 h exposure of eggs to either 30 ßM or 60 ßM BITC and transfer to water, percentage hatch at Day 14 was 51.3 ± 6.3% and 15.6 ± 1.4%, respectively. Each value was significantly less than the control percentage hatch (96.5 ± 0.2%). The same treatment method also resulted in decreased reproduction. The mean number of cysts per plant harvested 5 weeks after inoculation with control eggs (173.0 ± 12.1) was significantly greater than the numbers from plants inoculated with either 30 ^M (78.9 ± 8.2) or 60 ßM (38.3 ± 4.5) BITC treated eggs. Reduction of hatch and reproduction were strongly correlated, with r^ > 0.60 for both 30 ßM or 60 ßM BITC treatments. The effects of BITC were primarily on the early embryo. The percent of all embryos in the multicellular stage at Day 14 in control eggs was 4.9 ± 0.7%, but increased to 35.1 ± 4.3% (30 ßM) and 56.3 ± 4.5% (60 ßM) in BITC treated eggs. BITC has multiple effects on H. glycines, affecting both infective juvenile movement and embryonic development, and decreasing reproduction.

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“…Due to their capability to induce apoptosis, modulate signaling pathways and inhibit angiogenesis, isothiocyanates (ITCs) have shown a great promise as chemopreventive agents against various tumors in recent years [198]. Benzyl isothiocyanate (BITC) is a…”

Section: Benzyl Isothiocyanate (Bitc)mentioning

confidence: 99%

“…BITC suppresses the initiation and progression of a variety of cancers including lung, esophageal, forestomach, urinary bladder, mammary, liver, colon, and pancreatic tumors [198][199][200][201][202][203]. Various preclinical and mechanistic studies have supported the anticancer efficacy of BITC, and it has been found to suppress the growth of human pancreatic cancer cells both in vitro and in vivo.…”

Section: Accepted Manuscriptmentioning

confidence: 99%