Indole-3-carbinol: a plant hormone combatting cancer

A diet rich in cruciferous vegetables such as cauliflower, broccoli, and cabbage has long been considered healthy, and various epidemiological studies suggest that the consumption of cruciferous vegetables contributes to a cancer-protecting diet. While these vegetables contain a vast array of phytochemicals, the mechanism by which these vegetables counteract cancer is still largely unresolved. Numerous in situ studies have implicated indole-3-carbinol, a breakdown product of the glucosinolate indole-3-ylmethylglucosinolate, as one of the phytochemicals with anti-cancer properties. Indole-3-carbinol influences a range of cellular processes, but the mechanisms by which it acts on cancer cells are slowly being revealed. Recent studies on the role of indole-3-carbinol in Arabidopsis opens the door for cross-kingdom comparisons that can help in understanding the roles of this important phytohormone in both plant biology and combatting cancer.

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Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

Advances in Pharmacological Sciences ◽

10.1155/2014/832161 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 15

Author(s):

V. L. Maruthanila ◽

J. Poornima ◽

S. Mirunalini

Keyword(s):

Epidemiological Studies ◽

Cruciferous Vegetables ◽

Brussels Sprouts ◽

Anticancer Properties ◽

Depth Study ◽

Dimeric Product ◽

Indole Glucosinolate

Rising evidence provides credible support towards the potential role of bioactive products derived from cruciferous vegetables such as broccoli, cauliflower, kale, cabbage, brussels sprouts, turnips, kohlrabi, bok choy, and radishes. Many epidemiological studies point out thatBrassicavegetable protects humans against cancer since they are rich sources of glucosinolates in addition to possessing a high content of flavonoids, vitamins, and mineral nutrients. Indole-3-carbinol (I3C) belongs to the class of compounds called indole glucosinolate, obtained from cruciferous vegetables, and is well-known for tits anticancer properties. In particular, I3C and its dimeric product, 3,3′-diindolylmethane (DIM), have been generally investigated for their value against a number of human cancersin vitroas well asin vivo. This paper reviews an in-depth study of the anticancer activity and the miscellaneous mechanisms underlying the anticarcinogenicity thereby broadening its therapeutic marvel.

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Bioconcentration of glyphosate in wetland biofilms

10.1101/2020.08.03.234856 ◽

2020 ◽

Author(s):

Laura Beecraft ◽

Rebecca Rooney

Keyword(s):

Trophic Levels ◽

Breakdown Product ◽

Exposure Risk ◽

Surrounding Water ◽

Wetland Water ◽

Pesticides Exposure ◽

Wetland Water Quality ◽

Herbicide Glyphosate

AbstractWetland biofilms were exposed to the herbicide glyphosate via in situ field exposures and controlled microcosm experiments to measure bioconcentration and metabolism of glyphosate by biofilm organisms. Glyphosate concentrations in biofilms were orders of magnitude higher than the surrounding water, bioconcentration factors averaged 835 and 199 in field- and lab-exposed biofilms, respectively. Glyphosate in water where it had been detected in biofilms at field-exposed sites ranged from below detection (<0.001 ppm) up to 0.13 ppm. Glyphosate bioconcentration in biofilms was inversely proportional to levels in the surrounding water, and the retention kinetics were similar to both adsorption and enzymatic models. Microorganisms present in both the water and biofilms metabolized glyphosate to its primary breakdown product aminomethyl phosphonic acid (AMPA), with increased rates of breakdown in and around the biofilms. Photosynthetic efficiency of the algae within the biofilms was not affected by 24 h glyphosate controlled exposures. Our results demonstrate the role of biofilms in improving wetland water quality by removing contaminants like glyphosate, but also as a potential exposure route to higher trophic levels via consumption. Due to bioconcentration of pesticides, exposure risk to organisms consuming or living in biofilms may be much higher than indicated by concentrations in ambient water samples.

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ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer

Cells ◽

10.3390/cells10102509 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2509

Author(s):

Reiko Sugiura ◽

Ryosuke Satoh ◽

Teruaki Takasaki

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Tumor Cell Death ◽

Cancer Treatments ◽

Erk Activation ◽

Cellular Processes ◽

Dual Specificity ◽

Anti Cancer ◽

Dual Specificity Phosphatases

The RAF/MEK/ERK signaling pathway regulates diverse cellular processes as exemplified by cell proliferation, differentiation, motility, and survival. Activation of ERK1/2 generally promotes cell proliferation, and its deregulated activity is a hallmark of many cancers. Therefore, components and regulators of the ERK pathway are considered potential therapeutic targets for cancer, and inhibitors of this pathway, including some MEK and BRAF inhibitors, are already being used in the clinic. Notably, ERK1/2 kinases also have pro-apoptotic functions under certain conditions and enhanced ERK1/2 signaling can cause tumor cell death. Although the repertoire of the compounds which mediate ERK activation and apoptosis is expanding, and various anti-cancer compounds induce ERK activation while exerting their anti-proliferative effects, the mechanisms underlying ERK1/2-mediated cell death are still vague. Recent studies highlight the importance of dual-specificity phosphatases (DUSPs) in determining the pro- versus anti-apoptotic function of ERK in cancer. In this review, we will summarize the recent major findings in understanding the role of ERK in apoptosis, focusing on the major compounds mediating ERK-dependent apoptosis. Studies that further define the molecular targets of these compounds relevant to cell death will be essential to harnessing these compounds for developing effective cancer treatments.

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Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables

British Journal Of Nutrition ◽

10.1079/bjn2003917 ◽

2003 ◽

Vol 90 (3) ◽

pp. 687-697 ◽

Cited By ~ 108

Author(s):

S. A. McNaughton ◽

G. C. Marks

Keyword(s):

Dietary Exposure ◽

Epidemiological Studies ◽

Food Composition ◽

Biologically Active ◽

Glucosinolate Content ◽

Cruciferous Vegetables ◽

Dietary Intakes ◽

Active Constituents ◽

Food Composition Data

Evidence indicates that cruciferous vegetables are protective against a range of cancers with glucosinolates and their breakdown products considered the biologically active constituents. To date, epidemiological studies have not investigated the intakes of these constituents due to a lack of food composition databases. The aim of the present study was to develop a database for the glucosinolate content of cruciferous vegetables that can be used to quantify dietary exposure for use in epidemiological studies of diet–disease relationships. Published food composition data sources for the glucosinolate content of cruciferous vegetables were identified and assessed for data quality using established criteria. Adequate data for the total glucosinolate content were available from eighteen published studies providing 140 estimates for forty-two items. The highest glucosinolate values were for cress (389 mg/100 g) while the lowest values were for Pe-tsai chinese cabbage (20 mg/100 g). There is considerable variation in the values reported for the same vegetable by different studies, with a median difference between the minimum and maximum values of 5·8-fold. Limited analysis of cooked cruciferous vegetables has been conducted; however, the available data show that average losses during cooking are approximately 36 %. This is the first attempt to collate the available literature on the glucosinolate content of cruciferous vegetables. These data will allow quantification of intakes of the glucosinolates, which can be used in epidemiological studies to investigate the role of cruciferous vegetables in cancer aetiology and prevention.

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DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Cells ◽

10.3390/cells10020461 ◽

2021 ◽

Vol 10 (2) ◽

pp. 461

Author(s):

Eunji Kim ◽

Akash Ahuja ◽

Mi-Yeon Kim ◽

Jae Youl Cho

Keyword(s):

Protein Methylation ◽

Epigenetic Mechanisms ◽

Activator Protein 1 ◽

Cellular Processes ◽

Activator Protein ◽

Anti Cancer ◽

Anti Inflammatory ◽

Cell Signaling Networks ◽

Cancer Immunotherapies

Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling.

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The Role of Glucosinolates from Cruciferous Vegetables (Brassicaceae) in Gastrointestinal Cancers: From Prevention to Therapeutics

Pharmaceutics ◽

10.3390/pharmaceutics14010190 ◽

2022 ◽

Vol 14 (1) ◽

pp. 190

Author(s):

Catarina Melim ◽

Maria R. Lauro ◽

Isabel M. Pires ◽

Paulo J. Oliveira ◽

Célia Cabral

Keyword(s):

Cancer Colorectal ◽

Biologically Active ◽

Cruciferous Vegetables ◽

Brussels Sprouts ◽

Anti Cancer ◽

Gi Cancers ◽

The Stability ◽

Brassicaceae Family ◽

Related Mortality

The gastrointestinal (GI) tract is composed of rapidly renewing cells, which increase the likelihood of cancer. Colorectal cancer is one of the most frequently diagnosed GI cancers and currently stands in second place regarding cancer-related mortality. Unfortunately, the treatment of GI is limited, and few developments have occurred in the field over the years. With this in mind, new therapeutic strategies involving biologically active phytocompounds are being evaluated as anti-cancer agents. Vegetables such as broccoli, brussels sprouts, cabbage, cauliflower, and radish, all belonging to the Brassicaceae family, are high in dietary fibre, minerals, vitamins, carotenoids, polyphenols, and glucosinolates. The latter compound is a secondary metabolite characteristic of this family and, when biologically active, has demonstrated anti-cancer properties. This article reviews the literature regarding the potential of Cruciferous vegetables in the prevention and/or treatment of GI cancers and the relevance of appropriate compound formulations for improving the stability and bioaccessibility of the major Cruciferous compounds, with a particular focus on glucosinolates.

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Generation and Characterization of a New FRET-Based Ca2+ Sensor Targeted to the Nucleus

International Journal of Molecular Sciences ◽

10.3390/ijms22189945 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9945

Author(s):

Luisa Galla ◽

Nicola Vajente ◽

Diana Pendin ◽

Paola Pizzo ◽

Tullio Pozzan ◽

...

Keyword(s):

Fluorescent Protein ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Cellular Processes ◽

A Cell ◽

Dynamic Concentration ◽

Subcellular Compartmentalization

Calcium (Ca2+) exerts a pivotal role in controlling both physiological and detrimental cellular processes. This versatility is due to the existence of a cell-specific molecular Ca2+ toolkit and its fine subcellular compartmentalization. Study of the role of Ca2+ in cellular physiopathology greatly benefits from tools capable of quantitatively measuring its dynamic concentration ([Ca2+]) simultaneously within organelles and in the cytosol to correlate localized and global [Ca2+] changes. To this aim, as nucleoplasm Ca2+ changes mirror those of the cytosol, we generated a novel nuclear-targeted version of a Föster resonance energy transfer (FRET)-based Ca2+ probe. In particular, we modified the previously described nuclear Ca2+ sensor, H2BD3cpv, by substituting the donor ECFP with mCerulean3, a brighter and more photostable fluorescent protein. The thorough characterization of this sensor in HeLa cells demonstrated that it significantly improved the brightness and photostability compared to the original probe, thus obtaining a probe suitable for more accurate quantitative Ca2+ measurements. The affinity for Ca2+ was determined in situ. Finally, we successfully applied the new probe to confirm that cytoplasmic and nucleoplasmic Ca2+ levels were similar in both resting conditions and upon cell stimulation. Examples of simultaneous monitoring of Ca2+ signal dynamics in different subcellular compartments in the very same cells are also presented.

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Comparative Expression of P53 and Survivin Proteins in Phenylhydrazine-Induced Colon Cancer of Rats and the Role of Electromagnetic Field and Broccoli Extract

10.21203/rs.3.rs-531992/v1 ◽

2021 ◽

Author(s):

Aziz Awaad ◽

Mohamed A. Adly ◽

Medhat A. Abd ellatef ◽

Moshira M. Foad

Keyword(s):

Colon Cancer ◽

Electromagnetic Field ◽

Combined Therapy ◽

Low Frequency ◽

Survivin Expression ◽

Cancer Model ◽

Beneficial Effects ◽

Anti Cancer

Abstract Cancer constitutes as one of the most serious causes of death worldwide. For example, colon cancer is the second-most dangerous type of cancer, affecting both men and women. Recently, the application of electromagnetic field (EMF) in the treatment of cancer whether alone or in combination with other anti-cancer materials seems to be a promising therapy. Furthermore, broccoli extract which is rich with sulforaphane (sulfur-rich compound) previously used as one of anti-cancer materials. In this context, the current study aimed to investigate the potential beneficial effects of extremely low frequency-EMF (ELF-EMF) application alone and in combination with broccoli extract in the treatment and protection from cancer in phenylhydrazine (PHZ)-induced colon cancer model. To achieve our aims, the histolopathological abnormalities were investigated histologically and the comparative expression of P53 and survivin proteins were investigated immunohistochemically. This report revealed that PHZ injection was able to induce carcinogenicity in the large intestine of rats especially colon. The PHZ-injected group showed abnormal, biochemical, histological and immunohistochemical parameters. Histologically, the treated colon showed high-grade dysplastic lesions that are further considered as carcinoma-in-situ. The expression of P53 in the crypt of colon decreased significantly in the epithelial cells and lamina propria stroma. Contradictory, survivin expression increased in the same regions after animal exposed to PHZ. However, exposure of PHZ-injected animals to ELF-EMF or broccoli extract separately didn't ameliorate the abnormalities produced by PHZ completely. Interestingly, the combination between ELF-EMF and broccoli extract significantly mitigated the effects of PHZ and succeeded in suppressing tumor progression and normalize the expression of P53 and survivin expressions. This study provided important information about expression of important proteins during cancer stages and the role of combined therapy using EMFs and broccoli extract. Furthermore, the expression changes of P53 and survivin proteins might be used as markers in cancer diagnosis and treatment progress.

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The Role of APOSTART in Switching between Sexuality and Apomixis in Poa pratensis

Genes ◽

10.3390/genes11080941 ◽

2020 ◽

Vol 11 (8) ◽

pp. 941

Author(s):

Gianpiero Marconi ◽

Domenico Aiello ◽

Bryan Kindiger ◽

Loriano Storchi ◽

Alessandro Marrone ◽

...

Keyword(s):

Poa Pratensis ◽

Plant Biology ◽

Crop Species ◽

Mode Of Reproduction ◽

Sequence Characterized Amplified Region ◽

New Varieties ◽

Flower Tissue ◽

Detailed Work

The production of seeds without sex is considered the holy grail of plant biology. The transfer of apomixis to various crop species has the potential to transform plant breeding, since it will allow new varieties to retain valuable traits thorough asexual reproduction. Therefore, a greater molecular understanding of apomixis is fundamental. In a previous work we identified a gene, namely APOSTART, that seemed to be involved in this asexual mode of reproduction, which is very common in Poa pratensis L., and here we present a detailed work aimed at clarifying its role in apomixis. In situ hybridization showed that PpAPOSTART is expressed in reproductive tissues from pre-meiosis to embryo development. Interestingly, it is expressed early in few nucellar cells of apomictic individuals possibly switching from a somatic to a reproductive cell as in aposporic apomixis. Moreover, out of 13 APOSTART members, we identified one, APOSTART_6, as specifically expressed in flower tissue. APOSTART_6 also exhibited delayed expression in apomictic genotypes when compared with sexual types. Most importantly, the SCAR (Sequence Characterized Amplified Region) derived from the APOSTART_6 sequence completely co-segregated with apomixis.

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Apelin Effects Migration and Invasion Abilities of Colon Cancer Cells

Cells ◽

10.3390/cells7080113 ◽

2018 ◽

Vol 7 (8) ◽

pp. 113 ◽

Cited By ~ 4

Author(s):

Marta Podgórska ◽

Katarzyna Pietraszek-Gremplewicz ◽

Dorota Nowak

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Development ◽

Migration And Invasion ◽

Colon Cancer Cells ◽

Cellular Processes ◽

Anti Cancer ◽

Cancer Types ◽

Membrane Type

Colon cancer is one of the most common cancer types. Its positive correlation with general obesity has led to increasing amounts of research focusing on the role of adipokines in colon cancer development. Apelin is a peptide released by adipose tissue that could affect many cellular processes connected with carcinogenesis. In this study, we examined the role of apelin in the motility regulation of colon cancer cells. We showed that the effect of four different apelin peptides increased the ability of cancer cells to migrate and invade examined cells trough influencing migratory protrusions formation and actin cytoskeleton rearrangement. Additionally, using confocal microscopy, we noticed that apelin stimulated the proteolytic activity of cancer cells, especially increasing the level of membrane-type 1 matrix metalloprotease. Taken together, apelin increased the movement of colon cancer cells through several possible mechanisms. Moreover, better understanding the process through which apelin regulates cancer development is still necessary to the creation of novel anti-cancer therapy.

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