Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells

Božić, Dragica; Živančević, Katarina; Baralić, Katarina; Miljaković, Evica Antonijević; Djordjević, Aleksandra Buha; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

doi:10.1016/j.biopha.2023.114316

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…S12). In addition, the toxicity evaluation of ML-T7 using Derek Nexus, a famous commercial knowledge–based and regulator-approved toxicity prediction software ( 37 ), also supports the safety of ML-T7 in 56 test items (table S3). Preliminary physiochemical property analysis implied the potential of ML-T7 for oral bioavailability in humans (table S4).…”

Section: Resultsmentioning

confidence: 87%

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell–mediated antitumor immunotherapy in preclinical mouse models

Ma,

Tian,

Peng

et al. 2023

Sci. Transl. Med.

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T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC′ cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8 + cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells’ killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs’ functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC′ loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti–PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.

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Section: Resultsmentioning

confidence: 87%

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell–mediated antitumor immunotherapy in preclinical mouse models

Ma,

Tian,

Peng

et al. 2023

Sci. Transl. Med.

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“…In total, 11 SFN-related genes associated with chromosomal damage and 146 SFNrelated genes linked to skin diseases were observed, respectively, while SFN-triggered protein-protein interactions involved 490 and 1986 proteins associated with chromosomal damage and skin diseases, respectively. SFN was shown to have the ability to cause cell cycle disruption, apoptosis, and immune system activation, whereas chromosomal damage and/or skin illnesses such as dermatitis or psoriasis appeared to be its negative effects [83]. Furthermore, in another investigation, we proposed that SFN might also promote the overexpression of some genes (TIMP1, AURKA, CEP55) while suppressing others (CRYAB, PLCE1, and MMP28), thus leading to the advancement of colorectal cancer.…”

Section: Toxic Effectsmentioning

confidence: 89%

Sulforaphane—A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies

Baralić,

Živanović,

Marić

et al. 2024

Antioxidants

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Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models. SFN has also shown antidiabetic and anti-obesity effects, improving glucose tolerance and reducing fat accumulation. SFN’s ability to activate Nrf2, a transcription factor regulating oxidative stress and inflammation in cells, is a primary mechanism behind its anticancerogenic and antidiabetic effects. Its antioxidant, anti-inflammatory, and anti-apoptotic properties are also suggested to provide beneficial effects against neurodegenerative diseases. The potential health benefits of SFN have led to increased interest in its use as a dietary supplement or adjunct to chemotherapy, but there are insufficient data on its efficacy and optimal doses, as well as its safety. This review aims to present and discuss SFN’s potential in treating various diseases, such as cancer, diabetes, cardiovascular diseases, obesity, and neurodegenerative diseases, focusing on its mechanisms of action. It also summarizes studies on the pharmacological and toxicological potential of SFN in in vitro and animal models and explores its protective role against toxic compounds through in vitro and animal studies.

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“…Furthermore, they are rich in glucosinolates [14], which have anti-inflammatory and cardioprotective properties [15]. Additionally, these compounds are efficient chemopreventive agents both in vitro and in vivo [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Development of a Non-Destructive Tool Based on E-Eye and Agro-Morphological Descriptors for the Characterization and Classification of Different Brassicaceae Landraces

et al. 2023

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In recent years, Brassicaceae have piqued the interest of researchers due to their extremely rich chemical composition, particularly the abundance of antioxidants and anti-inflammatory compounds, as well as because of their antimutagenic and potential anticarcinogenic activity. Vegetables in this family can be found practically everywhere on the planet. In Italy, numerous varieties of Brassicaceae, as well as a diverse pool of local variants, are regularly cultivated. These landraces, which have a variety of peculiar features, have recently sparked increased interest, and the need to safeguard them to preserve genetic biodiversity has become a relevant topic. In the present study, eight distinct Brassicaceae folk varieties were studied using non-destructive tools (Multivariate Image analysis and agro-morphological descriptors). Eventually, the data were handled using explorative analysis (EA) and Soft Independent Modeling by Class Analogy (SIMCA). EA pointed out similarities/dissimilarities among the diverse investigated populations. SIMCA led to high sensitivity (>70%) in prediction (on the external test set) for seven (over eight) investigated classes. Although the investigated plants belong to different landraces, they bear strong similarities. This is mainly linked to the ability of Brassicaceae to hybridize. Despite this, the combination of colorgrams and SIMCA allowed for classifying samples with excellent accuracy.

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Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells

Cited by 6 publications

References 56 publications

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell–mediated antitumor immunotherapy in preclinical mouse models

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell–mediated antitumor immunotherapy in preclinical mouse models

Sulforaphane—A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies

Development of a Non-Destructive Tool Based on E-Eye and Agro-Morphological Descriptors for the Characterization and Classification of Different Brassicaceae Landraces

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