Cystathionine β-synthase overexpression drives metastatic dissemination in pancreatic ductal adenocarcinoma via inducing epithelial-to-mesenchymal transformation of cancer cells

Czikora, Ágnes; Erdélyi, Katalin; Ditrói, Tamás; Szántó, Noémi; Jurányi, Eszter Petra; Szanyi, Szilárd; Tóvári, József; Strausz, Tamás

doi:10.1016/j.redox.2022.102505

Cited by 13 publications

(5 citation statements)

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“…Taking into consideration the counsel featured in the paper by Zuhra et al [68] that it is often difficult to determine the observed biological effects related to compounds acting as a "CBS inhibitors", we conclude that in the triple-negative MDA-MB-231 cell line SAC may reduce the CBS expression, accompanied with the decrease in the cell growth, but further tests confirming this tendency are required to conclude the meaning of this change (such as testing the ability to generate H 2 S, cystathionine levels measurements, and determining CBS activity). Nevertheless, it seems that while overexpression of CBS is a feature that characterizes the cancer cells [66,69,70], it is a good prognosis that we observe the lowering of its expression upon S-allyl-L-cysteine exposure, and it may suggest beneficial SAC involvement against the triple-negative breast cancer cells. However, simultaneously we observe the elevated expression for CTH, that would describe quite the opposite prognosis.…”

Section: Discussionmentioning

confidence: 73%

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

Bentke-Imiolek,

Szlęzak,

Zarzycka

et al. 2024

Biomolecules

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S-allyl-L-cysteine (SAC) is a sulfur compound present in fresh garlic. The reference literature describes its anticancer, antioxidant and neuroprotective effects. Breast cancer is infamously known as one of the most commonly diagnosed malignancies among women worldwide. Its morbidity and mortality make it reasonable to complete and expand knowledge on this cancer’s characteristics. Hydrogen sulfide (H2S) and its naturally occurring donors are well-known investigation subjects for diverse therapeutic purposes. This study was conducted to investigate the SAC antiproliferative potential and effect on three enzymes involved in H2S metabolism: 3-mercaptopyruvate sulfurtransferase (MPST), cystathionine γ-lyase (CTH), and cystathionine β-synthase (CBS). We chose the in vitro cellular model of human breast adenocarcinomas: MCF-7 and MDA-MB-231. The expression of enzymes after 2, 4, 6, 8, and 24 h incubation with 2.24 mM, 3.37 mM, and 4.50 mM SAC concentrations was examined. The number of living cells was determined by the MTS assay. Changes in cellular plasma membrane integrity were measured by the LDH test. Expression changes at the protein level were analyzed using Western blot. A significant decrease in viable cells was registered for MCF-7 cells after all incubation times upon 4.50 mM SAC exposure, and after 6 and 24 h only in MDA-MB-231 upon 4.50 mM SAC. In both cell lines, the MPST gene expression significantly increased after the 24 h incubation with 4.50 mM SAC. S-allyl-L-cysteine had opposite effects on changes in CTH and CBS expression in both cell lines. In our research model, we confirmed the antiproliferative potential of SAC and concluded that our studies provided current information about the increase in MPST gene expression mediated by S-allyl-L-cysteine in the adenocarcinoma in vitro cellular model for the MCF-7 and MDA-MB-231 cell lines. Further investigation of this in vitro model can bring useful information regarding sulfur enzyme metabolism of breast adenocarcinoma and regulating its activity and expression (gene silencing) in anticancer therapy.

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Section: Discussionmentioning

confidence: 73%

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

Bentke-Imiolek,

Szlęzak,

Zarzycka

et al. 2024

Biomolecules

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“…These effects can be associated with several different processes. These include protection of protein function through protein persulfidation 49 , 50 , activation/inactivation of certain signalling pathways to counteract the effects of oxidative stress or the activation of Kelch-like ECH associated protein 1/Nrf2 system 47 – 49 , 51 , 52 .…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

Orján,

Kormányos,

Fűr

et al. 2023

Sci Rep

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Various organosulfur compounds, such as dimethyl trisulfide (DMTS), display anti-inflammatory properties. We aimed to examine the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein, ethanol-palmitoleic acid, or L-ornithine-HCl. DMTS treatments were administered subcutaneously. AP severity was assessed by pancreatic histological scoring, pancreatic water content, and myeloperoxidase activity measurements. The behaviour of animals was followed. Pancreatic heat shock protein 72 (HSP72) expression, sulfide, and protein persulfidation were measured. In vitro acinar viability, intracellular Ca2+ concentration, and reactive oxygen species production were determined. DMTS dose-dependently decreased the severity of AP. It declined the pancreatic infiltration of leukocytes and cellular damage in mice. DMTS upregulated the HSP72 expression during AP and elevated serum sulfide and low molecular weight persulfide levels. DMTS exhibited cytoprotection against hydrogen peroxide and AP-inducing agents. It has antioxidant properties and modulates physiological but not pathophysiological Ca2+ signalling. Generally, DMTS ameliorated AP severity and protected pancreatic acinar cells. Our findings indicate that DMTS is a sulfur donor with anti-inflammatory and antioxidant effects, and organosulfur compounds require further investigation into this potentially lethal disease.

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“…Conversely, inhibition of the STAT3 signaling pathway is associated with increased expression of E-cadherin ( 58 – 60 ), decreased expression of MMP-9 ( 61 – 63 ) and suppressed induction of EMT ( 58 ). Therefore, AGEs in MSpf may suppress EMT by decreased STAT3 signaling through the reduction of RAGE.…”

Section: Discussionmentioning

confidence: 99%

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

Yamamoto,

Shiburo,

Moriyama

et al. 2023

Oncol Rep

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Maple syrup is a natural sweetener consumed worldwide. Active ingredients of maple syrup possess antitumor effects; however, these ingredients are phenolic compounds. The present study aimed to investigate components other than phenolic compounds that may have antitumor effects against colorectal cancer (CRC). Cell proliferation assays demonstrated that treatment with the more than 10,000 molecular weight fraction significantly inhibited viability in DLD-1 cells. Therefore, we hypothesized that the protein components of maple syrup may be the active ingredients in maple syrup. We obtained protein components from maple syrup by ammonium sulfate precipitation, and treatment with the protein fraction of maple syrup (MSpf) was found to exhibit a potential antitumor effect. MSpf-treated DLD-1 colon adenocarcinoma cells exhibited significantly decreased proliferation, migration and invasion. In addition, upregulation of LC3A and E-cadherin and downregulation of MMP-9 expression levels were observed following MSpf treatment. Investigation of the components of MSpf suggested that it was primarily formed of advanced glycation end products (AGEs). Therefore, whether AGEs in MSpf affected the STAT3 pathway through the binding to its receptor, receptor of AGE (RAGE), was assessed. MSpf treatment was associated with decreased RAGE expression and STAT3 phosphorylation. Finally, to determine whether autophagy contributed to the inhibitory effect of cell proliferation following MSpf treatment, the effect of MSpf treatment on autophagy induction following bafilomycin A1 treatment, a specific autophagy inhibitor, was assessed. The inhibitory effect of MSpf treatment on cell proliferation was enhanced through the inhibition of autophagy by bafilomycin A1 treatment. These results suggested that AGEs in MSpf suppressed cell proliferation and epithelial-mesenchymal transition through inhibition of the STAT3 signaling pathway through decreased RAGE expression. Therefore, AGEs in MSpf may be potential compounds for the development of antitumor drugs for the treatment of CRC with fewer adverse effects compared with existing antitumor drugs.

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Cystathionine β-synthase overexpression drives metastatic dissemination in pancreatic ductal adenocarcinoma via inducing epithelial-to-mesenchymal transformation of cancer cells

Cited by 13 publications

References 50 publications

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

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