Synthesis and Characterization of Plumbagin S-Allyl Cysteine Ester: Determination of Anticancer Activity In Silico and In Vitro

Vijayan, Sudha; Loganathan, Chitra; Sakayanathan, Penislusshiyan; Palvannan, Thayumanavan

doi:10.1007/s12010-022-04079-0

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…In the normal mammary cell line MCF-10A, they observed that ABGE had no inhibitory effect on the growth of the cells. In other studies, plumbagin S-allyl cysteine (SAC) ester induced apoptosis in the breast cancer cell line (MCF-7) via oxidative stress, however, did not show toxicity towards the normal Vero cell line [61]. The results reported by other research teams, working with the selected cell model, correlate with our results, where for the MCF-7 line in response to the tested agent-SAC-we observe a reduction in cell viability in a dose-and time-dependent manner with simultaneous but quite moderate effect on reducing the number of viable cells in the MDA-MB-231 line.…”

Section: Discussionmentioning

confidence: 95%

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: 95%

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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Ab initio modeling of human IRS1 protein to find novel target to dock with drug MH to mitigate T2DM diabetes by insulin signaling

Singh,

Chaurasiya,

Kumar

2024

3 Biotech

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In silico analysis of highly disordered human IRS1 protein 3D structure to uncover new target for Metformin to ameliorate diabetes

Singh

Kumar

2023

Preprint

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IRSs are cytoplasmic-skeleton proteins. It facilitates RTK signaling through insulin/IGF-1, insulin receptor, and Src-homology-2-domains. IRS1 is a cytoplasmic adaptor protein that helps in cellular growth, glucose metabolism, proliferation, and differentiation. IRS1 is a disordered protein with a hard-to-predict active site. Here we used the ab-initiomodeling tool I-Tasser and Discovery studio/DogSite server to model and determine the active site of IRS1 human protein (mol. wt. 131590.97Da) respectively. Newly designed protein model submitted with PMDB Id–PM0082210. GRAVY index of IRS1 (-0.675) indicated surface protein-water interaction. Protparam tool instability index (75.22) demonstrated disorderedness combined with loops owing to prolines/glycines. After refinement Ramachandran plot showed that 88 percent of AAs were present in the allowed region. Novel mode protein has beta-sheet, loops, and beta-hairpin but fewer helixes. Overall IRS1 has 10-α-helices, 22-β-sheets, 20-β-hairpins, 5-β-bulges, 47-strands, 105-β-turns and 8-γ-turns. Docking studies suggest that MH binds with the novel active site of IRS1 to increase insulin signaling to target and cure the T2DM target molecule. MD-simulations have been done to reveal the protein–ligand complex stability and robustness. The discovered MH’s target site to cure T2DM, a worldwide problem could be further authenticated by in vitro and in vivo experiments to determine the efficiency of metformin hydrochloride to cure this worldwide disease.

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Synthesis and Characterization of Plumbagin S-Allyl Cysteine Ester: Determination of Anticancer Activity In Silico and In Vitro

Cited by 3 publications

References 76 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

Ab initio modeling of human IRS1 protein to find novel target to dock with drug MH to mitigate T2DM diabetes by insulin signaling

In silico analysis of highly disordered human IRS1 protein 3D structure to uncover new target for Metformin to ameliorate diabetes

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