Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines

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

doi:10.1016/j.biopha.2022.113137

Cited by 14 publications

(5 citation statements)

References 46 publications

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“…Collectively, HA-ADT inhibited HCC via promoting apoptosis through suppressing GSK-3β/AKT/β-catenin and inhibiting autophagy through suppressing TGF-β/Smad2/3 pathways ( Duan et al, 2023 ). The evidence indicates that exogenous H 2 S suppresses urothelial carcinoma cell proliferation through inducing cell autophagy and apoptosis ( Panza et al, 2022 ), which is inconsistent with the above study that exogenous H 2 S downregulates autophagy to inhibit HCC. This indicates that autophagy may have different activities in different tumors, and plays a dual role in promoting and inhibiting tumor development, according to the cellular environment.…”

Section: H 2 S Inhibits Hepatocellular Carcinomamentioning

confidence: 74%

The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma

Zhao,

Zhang,

et al. 2023

Front. Pharmacol.

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With an increasing worldwide prevalence, hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in the world. It is also the primary reason for cancer-related death in the world. The pathogenesis of HCC is complex, such as DNA methylation changes, immune regulatory disorders, cell cycle disorders, chromosomal instability, and so on. Although many studies have been conducted on HCC, the molecular mechanisms of HCC are not completely understood. At present, there is no effective treatment for HCC. Hydrogen sulfide (H2S) has long been regarded as a toxic gas with the smell of rotten eggs, but recent studies have shown that it is an important gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Increasing evidence indicates that H2S has multiple biological functions, such as anti-inflammation, anti-apoptosis, anti-oxidative stress, and so on. Recently, a lot of evidence has shown that H2S has a “double-edged sword” effect in HCC, but the mechanism is not fully understood. Here, we reviewed the progress on the role and mechanism of H2S in HCC in recent years, hoping to provide a theoretical reference for future related research.

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Section: H 2 S Inhibits Hepatocellular Carcinomamentioning

confidence: 74%

The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma

Zhao,

Zhang,

et al. 2023

Front. Pharmacol.

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“…Autophagy could be neutral, tumor-promoting, or tumorsuppressive in diferent contexts in cancer cells [87]. A recent study has shown that diallyl trisulfde, a characterized H 2 S donor, inhibits the proliferation of urothelial carcinoma cells by promoting apoptosis and inducing autophagy [88]. Our previous study has demonstrated that HA-ADT could suppress the progression of esophageal squamous cell carcinoma via apoptosis promotion and autophagy inhibition [89].…”

Section: Discussionmentioning

confidence: 99%

A Water-Soluble Hydrogen Sulfide Donor Suppresses the Growth of Hepatocellular Carcinoma via Inhibiting the AKT/GSK-3β/β-Catenin and TGF-β/Smad2/3 Signaling Pathways

Duan

Zhang

Dong

et al. 2023

Journal of Oncology

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Hepatocellular carcinoma (HCC) is a disease with high morbidity, high mortality, and low cure rate. Hyaluronic acid (HA) is widely adopted in tissue engineering and drug delivery. 5-(4-Hydroxyphenyl)-3H-1, 2-dithiol-3-thione (ADT-OH) is one of commonly used H2S donors. In our previous study, HA-ADT was designed and synthesized via coupling of HA and ADT-OH. In this study, compared with sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor), HA-ADT showed stronger inhibitory effect on the proliferation, migration, invasion, and cell cycle of human HCC cells. HA-ADT promoted apoptosis by suppressing the expressions of phospho (p)-protein kinase B (PKB/AKT), p‐glycogen synthase kinase‐3β (GSK-3β), p‐β‐catenin, and also inhibited autophagy via the downregulation of the protein levels of p‐Smad2, p‐Smad3, and transforming growth factor‐β (TGF‐β) in human HCC cells. Moreover, HA-ADT inhibited HCC xenograft tumor growth more effectively than both NaHS and GYY4137. Therefore, HA-ADT can suppress the growth of HCC cells by blocking the AKT/GSK-3β/β-catenin and TGF‐β/Smad2/3 signaling pathways. HA-ADT and its derivatives may be developed as promising antitumor drugs.

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“…Moreover, at this concentration erucin also promotes a significant apoptosis concomitantly enhancing the expression of key genes and proteins (BECN1, LC3, ULK1, ATG13, BNIP3) triggering and driving autophagy. Thus, erucin acts on both autophagy and apoptosis, with these functions being intimately intertwined to control, among numerous processes, the cell fate [ 34 , 35 ]; this approach represents a promising target in many types of cancer. Intracellular imbalance in ROS production is one of the major pathological mechanisms underpinning tumor initiation and metastatic progression [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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

Bello

Smimmo

Bianca

et al. 2023

IJMS

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Breast cancer is the most frequent form of cancer occurring in women of any age. Among the different types, the triple-negative breast cancer (TNBC) subtype is recognized as the most severe form, being associated with the highest mortality rate. Currently, there are no effective treatments for TNBC. For this reason, the research of novel therapeutics is urgently needed. Natural products and their analogs have historically made a major contribution to pharmacotherapy and the treatment of various human diseases, including cancer. In this study, we explored the potential anti-cancer effects of erucin, the most abundant H2S-releasing isothiocyanate present in arugula (Eruca sativa) in MDA-MB-231 cells, a validated in vitro model of TNBC. We found that erucin, in a concentration-dependent manner, significantly inhibited MDA-MB-231 cell proliferation by inducing apoptosis and autophagy. Additionally, erucin prevented intracellular ROS generation promoting the expression of key antioxidant genes and halted MDA-MB-231 cell migration, invasion, and colony formation. In conclusion, using a cellular and molecular biology approach, we show that the consumption of erucin could represent a novel and promising strategy for intervention against TNBC.

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Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines

Cited by 14 publications

References 46 publications

The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma

The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma

A Water-Soluble Hydrogen Sulfide Donor Suppresses the Growth of Hepatocellular Carcinoma via Inhibiting the AKT/GSK-3β/β-Catenin and TGF-β/Smad2/3 Signaling Pathways

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

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