Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells

Santos, Patrick Wellington da Silva; Machado, Ana Rita Thomazela; Grandis, Rone Aparecido De; Ribeiro, Diego Luís; Tuttis, Katiuska; Morselli, Marco; Aissa, Alexandre Ferro; Pellegrini, Matteo; Antunes, Lusânia Maria Greggi

doi:10.1016/j.fct.2019.111047

Cited by 58 publications

(29 citation statements)

References 81 publications

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“…Therefore, according to the LASSO regression method, we determined 24 DEPs: MKI67, LOXL2, PLIN4, IL33, MDK, P4HA2, AKR7A3, PLCXD3, CDK1, SRPX, PRPH, PRKAR2B, P4HA1, CALML3, SFN, DES, PHYHD1, GPD1, AADAT, PGM5, ADH1C, FBP2, ENO3, EHD3. In accordance with the above classi cation, among the 24 proteins, CDK1, SFN, PRKAR2B, MKI67 and MDK were involved in the cell cycle; 16,23,38 AKR7A3, GPD1, ENO3, FBP2, AADAT, PGM5 and ADH1C were involved in cell metabolism; 25,27,39 LOXL2, P4HA1, P4HA2, SPRX, DES, PRPH and CALML3 were involved in construction and regulation of extracellular matrix. [40][41][42] And most of these proteins have been identi ed to contribute to prognosis of many cancers.…”

Section: Discussionmentioning

confidence: 59%

Development of Prognostic Signature Based on Pan-cancer Proteomics

Huang

Weng

Xiang

et al. 2020

Preprint

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Background: Utilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. Based on CPTAC (Clinical Proteomic Tumor Analysis Consortium) which has generated extensive proteomics data of the vast majority of tumors, we can perform a proteomic pan-carcinoma analysis.Methods: The proteomics data and clinical features of cancer patients were collected from CPTAC. We screened 69 differentially expressed proteins with R software. GO and KEGG analysis were performed to clarify the function of these proteins. The DEPs-based prognostic model was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model. The time-dependent receiver operating characteristics analysis was used to evaluate the ability of the prognostic model to predict overall survival.Results: A total of 69 differentially expressed proteins were screened in five different types of cancers: hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), children's brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC) and uterine corpus endometrial carcinoma (UCEC). Furthermore, the differentially expressed proteins were related to cell metabolism, cell proliferation and extracellular matrix. Then 24 DEPs-based classifiers for predicting OS was developed by LASSO-Cox regression model in training cohort, which was validated in validation cohort. Conclusions: In the present study, we identified DEPs-based survival-predictor model to predict most cancers. We are the first group to utilize proteomics to construct a pan-cancer prognosis model, which could accurately and effectively predict the survival rate of most cancers.

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Section: Discussionmentioning

confidence: 59%

Development of Prognostic Signature Based on Pan-cancer Proteomics

Huang

Weng

Xiang

et al. 2020

Preprint

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“…Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles ( 43 , 44 ). Our current study showed that DH has relative stronger inhibitory effect on fast-growing cells, which indicates that it may also regulate the proliferation of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis

Bian

Wang

et al. 2020

Front. Immunol.

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Experimental autoimmune uveitis (EAU) is a CD4 + T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4 + T cell biology and hence ameliorates the development of CD4 + T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4 + T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4 + T cells. Instead, it significantly suppressed the proliferation of conventional CD4 + T cells both in vitro and in vivo. Mechanistic study showed that DH-treated CD4 + T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4 + T cells. Taken together, the current study indicates that DH-mediated suppression of CD4 + T cell proliferation may provide a promising therapeutic strategy for treating CD4 + T cell-mediated diseases.

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“…Over 10,000 phytochemicals have been identified worldwide [ 144 , 145 ]. Furthermore, genistein (from soybeans and soy products) [ 146 , 147 , 148 ], lycopene (such as from tomatoes, red carrots, watermelons, grapefruits, and papayas) [ 149 , 150 , 151 ], brassinin (from cruciferous vegetables) [ 152 , 153 , 154 ], sulforaphane (from asparagus) [ 155 , 156 , 157 ], indole-3-carbinol (from broccoli) [ 158 , 159 , 160 ], and resveratrol (from grapes, peanuts, peanut butter, red wines) [ 161 , 162 , 163 , 164 , 165 ] are being studied in preclinical or clinical trials for cancer chemoprevention.…”

Section: Overview Of Phytochemicalsmentioning

confidence: 99%

The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence

Lee

Tseng

2020

Biomolecules

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The etiological factors of oral cancer are complex including drinking alcohol, smoking tobacco, betel quid chewing, human papillomavirus infection, and nutritional deficiencies. Understanding the molecular mechanism of oral cancer is vital. The traditional treatment for patients with oral squamous cell carcinoma (e.g., surgery, radiotherapy, and chemotherapy) and targeted molecular therapy still have numerous shortcomings. In recent years, the use of phytochemical factors to prevent or treat cancer has received increasing attention. These phytochemicals have little or no toxicity against healthy tissues and are thus ideal chemopreventive agents. However, phytochemicals usually have low water solubility, low bioavailability, and insufficient targeting which limit therapeutic use. Numerous studies have investigated the development of phytochemical delivery systems to address these problems. The present article provides an overview of oral cancer including the etiological factors, diagnosis, and traditional therapy. Furthermore, the classification, dietary sources, anticancer bioactivity, delivery system improvements, and molecular mechanisms against oral cancer of phytochemicals are also discussed in this review.

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Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells

Cited by 58 publications

References 81 publications

Development of Prognostic Signature Based on Pan-cancer Proteomics

Development of Prognostic Signature Based on Pan-cancer Proteomics

Dracocephalum heterophyllum (DH) Exhibits Potent Anti-Proliferative Effects on Autoreactive CD4+ T Cells and Ameliorates the Development of Experimental Autoimmune Uveitis

The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence

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