Suppression of multiple processes relevant to cancer progression by benzyl isothiocyanate may result from the inhibition of Aurora A kinase activity

Yu, Tzu-Tung; Chang, Meng-Ya; Hsieh, Yi-Jen; Chang, Chih-Jui

doi:10.1039/d0fo01565b

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…Indeed, G2/M-phase arrest in presence of AITC has been observed in T24 [ 18 ] and UMUC3 cell cultures by others [ 19 ]. G2/M-phase arrest has also found in cell cultures from further tumor entities treated with BITC, AITC, or PEITC [ 23 , 24 , 25 ]. Presumably, G2/M-phase cell cycle arrest observed here might be mainly responsible for the loss of bladder cancer cell growth and proliferation resulting from ITC treatment.…”

Section: Discussionmentioning

confidence: 99%

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt–mTOR and Cyclin–CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines

Rutz

Maxeiner

Grein

et al. 2022

IJMS

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Combined cisplatin–gemcitabine treatment causes rapid resistance development in patients with advanced urothelial carcinoma. The present study investigated the potential of the natural isothiocyanates (ITCs) allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to suppress growth and proliferation of gemcitabine- and cisplatin-resistant bladder cancer cells lines. Sensitive and gemcitabine- and cisplatin-resistant RT112, T24, and TCCSUP cells were treated with the ITCs, and tumor cell growth, proliferation, and clone formation were evaluated. Apoptosis induction and cell cycle progression were investigated as well. The molecular mode of action was investigated by evaluating cell cycle-regulating proteins (cyclin-dependent kinases (CDKs) and cyclins A and B) and the mechanistic target of the rapamycin (mTOR)-AKT signaling pathway. The ITCs significantly inhibited growth, proliferation and clone formation of all tumor cell lines (sensitive and resistant). Cells were arrested in the G2/M phase, independent of the type of resistance. Alterations of both the CDK–cyclin axis and the Akt–mTOR signaling pathway were observed in AITC-treated T24 cells with minor effects on apoptosis induction. In contrast, AITC de-activated Akt–mTOR signaling and induced apoptosis in RT112 cells, with only minor effects on CDK expression. It is concluded that AITC, BITC, and PEITC exert tumor-suppressive properties on cisplatin- and gemcitabine-resistant bladder cancer cells, whereby the molecular action may differ among the cell lines. The integration of these ITCs into the gemcitabine-/cisplatin-based treatment regimen might optimize bladder cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt–mTOR and Cyclin–CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines

Rutz

Maxeiner

Grein

et al. 2022

IJMS

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“…On the one hand, SREBP-1 plays and progression of HCC and is an ideal intervention target for HCC treatment. Small molecule inhibitors are an ideal mode of action for specific targets (71)(72)(73)(74). The existing SREBP-1 small molecule inhibitors are mainly Betulin, Pseudoprotodioscin and Fatostatin (75)(76)(77).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

2021

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Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

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“…The mechanistic insights highlighted that BITC treatment resulted in the increased production of ROS, which led to caspase-3 activation in HeLa cells. BITC exposure to HeLa and MRC-5 cells decreased cell viability in a time- and dose-dependent manner [ 99 ]. Furthermore, BITC treatment was more toxic to the dividing cells, owing to reduced phosphorylation of Aurora A [ 99 ].…”

Section: Impacts Of Isothiocyanates On Female-specific Cancersmentioning

confidence: 99%

“…BITC exposure to HeLa and MRC-5 cells decreased cell viability in a time- and dose-dependent manner [ 99 ]. Furthermore, BITC treatment was more toxic to the dividing cells, owing to reduced phosphorylation of Aurora A [ 99 ]. BITC-treated ovarian cancer cells undergo growth and proliferation inhibition in a dose- and time-dependent manner, seemingly due to the induction of DNA fragmentation, condensation, and eventually apoptosis induction [ 130 ].…”

Section: Impacts Of Isothiocyanates On Female-specific Cancersmentioning

confidence: 99%

“…Of note, it has been envisaged that BITC treatment on MCF-7 and MDA-MB-231 cells showed cell cycle arrest, which occurred in response to the down-regulation of important cell cycle regulators such as cyclin B1, CDK1, and Cdc25C [ 88 ]. Amongst the various plausible reasons, BITC-mediated cytotoxicity on cervical cancer cells may be due to the perturbation in the cell cycle; interestingly, accumulation of cells in the G2 and M phase was observed in a dose- and time-dependent manner in both cell lines (HeLa and MRC-5) following treatment with BITC, which may plausibly be attributed to the inhibition of Aurora A, polo-like kinase (PLK1) but not Aurora B activity thereof [ 99 ]. Interestingly, BITC treatment for ovarian cancer cells led to the perturbation in the cell cycle progression, which increased the percentage of cells in the G2 and M phase; the mechanism of action behind the activity of BITC to cause G2/M cell cycle arrest was possibly due to the decreased Akt signaling [ 130 ].…”

Section: Impacts Of Isothiocyanates On Female-specific Cancersmentioning

confidence: 99%

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Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers

Shoaib

Khan

Alsharif

et al. 2023

Cancers

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Gynecological cancers are the most commonly diagnosed malignancies in females worldwide. Despite the advancement of diagnostic tools as well as the availability of various therapeutic interventions, the incidence and mortality of female-specific cancers is still a life-threatening issue, prevailing as one of the major health problems worldwide. Lately, alternative medicines have garnered immense attention as a therapeutic intervention against various types of cancers, seemingly because of their safety profiles and enhanced effectiveness. Isothiocyanates (ITCs), specifically sulforaphane, benzyl isothiocyanate, and phenethyl isothiocyanate, have shown an intriguing potential to actively contribute to cancer cell growth inhibition, apoptosis induction, epigenetic alterations, and modulation of autophagy and cancer stem cells in female-specific cancers. Additionally, it has been shown that ITCs plausibly enhance the chemo-sensitization of many chemotherapeutic drugs. To this end, evidence has shown enhanced efficacy in combinatorial regimens with conventional chemotherapeutic drugs and/or other phytochemicals. Reckoning with these, herein, we discuss the advances in the knowledge regarding the aspects highlighting the molecular intricacies of ITCs in female-specific cancers. In addition, we have also argued regarding the potential of ITCs either as solitary treatment or in a combinatorial therapeutic regimen for the prevention and/or treatment of female-specific cancers. Hopefully, this review will open new horizons for consideration of ITCs in therapeutic interventions that would undoubtedly improve the prognosis of the female-specific cancer clientele. Considering all these, it is reasonable to state that a better understanding of these molecular intricacies will plausibly provide a facile opportunity for treating these female-specific cancers.

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Suppression of multiple processes relevant to cancer progression by benzyl isothiocyanate may result from the inhibition of Aurora A kinase activity

Abstract: Cruciferous vegetables are good sources of phytochemicals that have potential to prevent cancer. Benzyl isothiocyanate (BITC) is the hydrolysis product of glucosinolates that are especially rich in crufiferous vegetables. The...

Cited by 8 publications

References 52 publications

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt–mTOR and Cyclin–CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt–mTOR and Cyclin–CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers

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