Erucin, an H2S-Releasing Isothiocyanate, Exerts Anticancer Effects in Human Triple-Negative Breast Cancer Cells Triggering Autophagy-Dependent Apoptotic Cell Death

Bello, Ivana; Smimmo, Martina; Bianca, Roberta d’Emmanuele di Villa; Bucci, Mariarosaria; Cirino, Giuseppe; Panza, Elisabetta; Brancaleone, Vincenzo

doi:10.3390/ijms24076764

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…Furthermore, ERU exhibited a cardioprotective effect in an in vivo model of I/R injury through direct persulfidation of mitoKv7.4 channels, unequivocally confirming the link between the cardioprotective effects of ERU and the H 2 S released from the isothiocyanate moiety [33]. Moreover, ERU was found to inhibit the tumor growth in human triple-negative breast cancer cells [52] as well as in a breast cancer cell xenograft mouse model; interestingly, in this case a regulation of mitochondrial fission/fusion emerges, in particular with the translocation of cofilin and Drp1 and consequent cell apoptosis [53].…”

Section: Discussionsupporting

confidence: 52%

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Flori,

Montanaro,

Pagnotta

et al. 2023

Biomedicines

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Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H2S), an endogenous pleiotropic gasotransmitter responsible for anti-ischemic cardioprotective effects also through the involvement of mitoK channels. Erucin (ERU) is a natural isothiocyanate resulting from the enzymatic hydrolysis of glucosinolates (GSLs) present in Eruca sativa Mill. seeds, an edible plant of the Brassicaceae family. In this experimental work, the specific involvement of mitoKATP channels in the cardioprotective effect induced by ERU was evaluated in detail. An in vivo preclinical model of acute myocardial infarction was reproduced in rats to evaluate the cardioprotective effect of ERU. Diazoxide was used as a reference compound for the modulation of potassium fluxes and 5-hydroxydecanoic acid (5HD) as a selective blocker of KATP channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoKATP channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoKATP channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.

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Section: Discussionsupporting

confidence: 52%

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Flori,

Montanaro,

Pagnotta

et al. 2023

Biomedicines

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“…The effect has been reported to be concentration-dependent [7]. The effect of H 2 S and H 2 S donors in cancer has been widely reported in several experimental studies and, similarly to what observed for Met, it seems to act via several mechanisms ranging from the alteration of the cell cycle and the DNA replication pathway [47] to apoptotic cell death [48] induced via the inhibition of ERK1/2 phosphorylation [20], the attenuation of ferroptosis [49] or autophagy [19]. Among the different H 2 S donors, isothiocyanates are well known for their peculiar epigenetic anti-cancer effect, linked to their ability to inhibit histone deacetylases (HDACs) enzymes [50,51].…”

Section: Discussionmentioning

confidence: 71%

Anti-Proliferative Properties of the Novel Hybrid Drug Met-ITC, Composed of the Native Drug Metformin with the Addition of an Isothiocyanate H2S Donor Moiety, in Different Cancer Cell Lines

Citi,

Barresi,

Piragine

et al. 2023

IJMS

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Metformin (Met) is the first-line therapy in type 2 diabetes mellitus but, in last few years, it has also been evaluated as anti-cancer agent. Several pathways, such as AMPK or PI3K/Akt/mTOR, are likely to be involved in the anti-cancer Met activity. In addition, hydrogen sulfide (H2S) and H2S donors have been described as anti-cancer agents affecting cell-cycle and inducing apoptosis. Among H2S donors, isothiocyanates are endowed with a further anti-cancer mechanism: the inhibition of the histone deacetylase enzymes. On this basis, a hybrid molecule (Met-ITC) obtained through the addition of an isothiocyanate moiety to the Met molecule was designed and its ability to release Met has been demonstrated. Met-ITC exhibited more efficacy and potency than Met in inhibiting cancer cells (AsPC-1, MIA PaCa-2, MCF-7) viability and it was less effective on non-tumorigenic cells (MCF 10-A). The ability of Met-ITC to release H2S has been recorded both in cell-free and in cancer cells assays. Finally, its ability to affect the cell cycle and to induce both early and late apoptosis has been demonstrated on the most sensitive cell line (MCF-7). These results confirmed that Met-ITC is a new hybrid molecule endowed with potential anti-cancer properties derived both from Met and H2S.

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“…Also, erucin demonstrated to have anti-proliferative activity in human lung adenocarcinoma A549 cells through the induction of p53, p21 and PARP-1 cleavage [71]. Recently, erucin was demonstrated to have anticancer effects in an in vitro model of triple-negative breast cancer (TNBC) subtype by inducing apoptosis and autophagy, having also antimetastatic activity [72]. In an in vitro model of renal cancer, erucin induced a concentration-dependent decrease in cell viability and cell-cycle arrest at G2/Mitosis [24].…”

Section: Glucoerucin (Ge) and Erucinmentioning

confidence: 99%

Absorption and Excretion of Glucosinolates and Isothiocyanates after Ingestion of Broccoli (Brassica oleracea L. var italica) Leaf Flour in Mice: A Preliminary Study

Martins,

Ferreira,

Colaço

et al. 2023

Nutraceuticals

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During the harvesting of the broccoli plant, the leaves are discarded, being considered a by-product that may be up to 47% of total broccoli biomass, representing a large amount of wasted material. The use of broccoli leaves is of great interest in the sense that this wasted material is rich in health promoter compounds, such as isothiocyanates. In this study, C57BL/6J mice ingested 790 mg/kg broccoli leaf flour, and the presence of glucosinolates and isothiocyanates in the plasma, liver, kidney, adipose tissue, faeces and urine was analysed at 1, 2, 4, 8, 12 and 24 h post-ingestion. In plasma, only glucoerucin (GE), glucobrassicin (GB), sulforaphane (SFN) and indol-3-carbinol (I3C) were detected, and all four compounds peaked between 4 and 8 h after ingestion. The compounds SFN, SFN-glutathione (SFN-GSH), SFN–cysteine (SFN-CYS) and SFN-N-acetyl-cysteine (SFN-NAC) were excreted in faeces at high levels, while glucoraphanin (GR), the precursor of SFN, was not detected in any biological samples other than urine. In the liver, the compounds GE, SFN-CYS, SFN-NAC and I3C were detected, while in the kidney, only GE, GB and SFN-GSH were present. None of the glucosinolates and isothiocyanates analysed were detected in fat tissue. These results demonstrate that glucosinolates and their derivatives were absorbed into the bloodstream and were bioavailable after ingestion of powdered broccoli leaves.

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Erucin, an H2S-Releasing Isothiocyanate, Exerts Anticancer Effects in Human Triple-Negative Breast Cancer Cells Triggering Autophagy-Dependent Apoptotic Cell Death

Cited by 9 publications

References 38 publications

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Anti-Proliferative Properties of the Novel Hybrid Drug Met-ITC, Composed of the Native Drug Metformin with the Addition of an Isothiocyanate H2S Donor Moiety, in Different Cancer Cell Lines

Absorption and Excretion of Glucosinolates and Isothiocyanates after Ingestion of Broccoli (Brassica oleracea L. var italica) Leaf Flour in Mice: A Preliminary Study

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