Inhibition of phosphatidylinositide 3-kinase ameliorates antiproliferation by benzyl isothiocyanate in human colon cancer cells

Liu, Xiaoyang; Chiaki, Takano; Shimizu, Tomomi; Yokobe, Shintaro; Abe-Kanoh, Naomi; Zhu, Beiwei; Nakamura, Toshiyuki; Munemasa, Shintaro; Murata, Yoshiyuki; Nakamura, Yoshimasa

doi:10.1016/j.bbrc.2017.07.078

Cited by 22 publications

(28 citation statements)

References 26 publications

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“…Combinatorial treatment of genistein and indole-3-carbinol synergistically induced apoptosis of HCT 116 cells [ 92 ]. Benzyl isothiocyanate (BITC), an organosulfur compound, suppressed the viability of HCT 116 cells and activated the PI3K/Akt/forkhead box O pathway, which influences drug resistance in various human cancer cells [ 93 ]. A combination treatment with an inhibitor of the PI3K/Akt/forkhead box O pathway potentiated cell death of colorectal cancer cells induced by BITC [ 93 ].…”

Section: Anti-tumor Activity Of Plant Metabolites In Various Maligmentioning

confidence: 99%

“…Benzyl isothiocyanate (BITC), an organosulfur compound, suppressed the viability of HCT 116 cells and activated the PI3K/Akt/forkhead box O pathway, which influences drug resistance in various human cancer cells [ 93 ]. A combination treatment with an inhibitor of the PI3K/Akt/forkhead box O pathway potentiated cell death of colorectal cancer cells induced by BITC [ 93 ]. Sulforaphane, another isothiocyanate, has an anticancer effect on the human colon cancer cell line HT-29.…”

Section: Anti-tumor Activity Of Plant Metabolites In Various Maligmentioning

confidence: 99%

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Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites

Shin

Moon

Kim

et al. 2018

IJMS

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A variety of malignant cancers affect the global human population. Although a wide variety of approaches to cancer treatment have been studied and used clinically (surgery, radiotherapy, chemotherapy, and immunotherapy), the toxic side effects of cancer therapies have a negative impact on patients and impede progress in conquering cancer. Plant metabolites are emerging as new leads for anti-cancer drug development. This review summarizes these plant metabolites with regard to their structures and the types of cancer against which they show activity, organized by the organ or tissues in which each cancer forms. This information will be helpful for understanding the current state of knowledge of the anti-cancer effects of various plant metabolites against major types of cancer for the further development of novel anti-cancer drugs.

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Section: Anti-tumor Activity Of Plant Metabolites In Various Maligmentioning

confidence: 99%

Section: Anti-tumor Activity Of Plant Metabolites In Various Maligmentioning

confidence: 99%

Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites

Shin

Moon

Kim

et al. 2018

IJMS

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“…ITCs have been shown to inhibit cell proliferation by inducing cell cycle arrest and apoptosis in various cancer cells. ( 5 , 59 – 66 ) The antiproliferative effect of ITCs in human non-small lung cancer A549 cells followed the order of BITC > PEITC > SFN. ( 39 ) The same order of potency is found in the binding affinities of ITCs to tubulin, the inhibition of tubulin polymerization in vitro , the disruption of microtubule networks, the induction of tubulin-containing protein aggregates, and degradation of tubulin through ubiquitin-proteasome system, ( 39 , 67 ) strongly suggesting the physiological relevance of ITC binding to tubulin.…”

Section: Potential Targets Of Itcs and Their Physiological Relevancementioning

confidence: 99%

“…( 80 ) The PTP1B inhibition may play an important role in the modulation of the insulin receptor/PI3K/Akt survival pathway by BITC. ( 66 ) In addition, the Cys112 of GSTA1, playing a key role in the catalytic activity, has been identified as a covalent modification target of PEITC by high-resolution MS. ( 81 )…”

Section: Potential Targets Of Itcs and Their Physiological Relevancementioning

confidence: 99%

Physiological relevance of covalent protein modification by dietary isothiocyanates

Nakamura

Abe-Kanoh

Nakamura

2018

J. Clin. Biochem. Nutr.

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Isothiocyanates (ITCs), naturally occurring in abundance in cruciferous vegetables, are the most well-studied organosulfur compounds having an electrophilic reactivity. ITCs have been accepted as major ingredients of these vegetables that afford their health promoting potentials. ITCs are able to modulate protein functions related to drug-metabolizing enzymes, transporters, kinases and phosphatases, etc. One of the most important questions about the molecular basis for the health promoting effects of ITCs is how they modulate cellular target proteins. Although the molecular targets of ITCs remains to be validated, dietary modulation of the target proteins via covalent modification by ITCs should be one of the promising strategies for the protection of cells against oxidative and inflammatory damage. This review discusses the plausible target proteins of dietary ITCs with an emphasis on possible involvement of protein modification in their health promoting effects. The fundamental knowledge of ITCs is also included with consideration of the chemistry, intracellular behavior, and metabolism.

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“…Moreover, recent studies emphasize that modification of cellular proteins via direct covalent binding of ITCs for an early event in anticarcinogenic activities such as cell cycle arrest or apoptosis induction [ 19 , 21 , 22 , 27 ]. Interestingly, more recently, ITSs have been found to inactivate PTP1B [ 28 – 30 ], which has a reactive cysteine residue at the catalytic center [ 29 ]. However, the mechanism underlying these effects was not clarified fully.…”

Section: Introductionmentioning

confidence: 99%

Phenethyl isothiocyanate activates leptin signaling and decreases food intake

et al. 2018

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Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity.

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Inhibition of phosphatidylinositide 3-kinase ameliorates antiproliferation by benzyl isothiocyanate in human colon cancer cells

Cited by 22 publications

References 26 publications

Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites

Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites

Physiological relevance of covalent protein modification by dietary isothiocyanates

Phenethyl isothiocyanate activates leptin signaling and decreases food intake

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