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Mohan CD, Shanmugam MK, Gowda SGS, Chinnathambi A, Rangappa KS, Sethi G. c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155379. [PMID: 38503157 DOI: 10.1016/j.phymed.2024.155379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/03/2024] [Accepted: 01/17/2024] [Indexed: 03/21/2024]
Abstract
BACKGROUND c-MET is a receptor tyrosine kinase which is classically activated by HGF to activate its downstream signaling cascades such as MAPK, PI3K/Akt/mTOR, and STAT3. The c-MET modulates cell proliferation, epithelial-mesenchymal transition (EMT), immune response, morphogenesis, apoptosis, and angiogenesis. The c-MET has been shown to serve a prominent role in embryogenesis and early development. The c-MET pathway is deregulated in a broad range of malignancies, due to overexpression of ligands or receptors, genomic amplification, and MET mutations. The link between the deregulation of c-MET signaling and tumor progression has been well-documented. Overexpression or overactivation of c-MET is associated with dismal clinical outcomes and acquired resistance to targeted therapies. Since c-MET activation results in the triggering of oncogenic pathways, abrogating the c-MET pathway is considered to be a pivotal strategy in cancer therapeutics. Herein, an analysis of role of the c-MET pathway in human cancers and its relevance in bone metastasis and therapeutic resistance has been undertaken. Also, an attempt has been made to summarize the inhibitory activity of selected natural compounds towards c-MET signaling in cancers. METHODS The publications related to c-MET pathway in malignancies and its natural compound modulators were obtained from databases such as PubMed, Scopus, and Google Scholar and summarized based on PRISMA guidelines. Some of the keywords used for extracting relevant literature are c-MET, natural compound inhibitors of c-MET, c-MET in liver cancer, c-MET in breast cancer, c-MET in lung cancer, c-MET in pancreatic cancer, c-MET in head and neck cancer, c-MET in bone metastasis, c-MET in therapeutic resistance, and combination of c-MET inhibitors and chemotherapeutic agents. The chemical structure of natural compounds was verified in PubChem database. RESULTS The search yielded 3935 publications, of which 195 reference publications were used for our analysis. Clinical trials were referenced using ClinicalTrials.gov identifier. The c-MET pathway has been recognized as a prominent target to combat the growth, metastasis, and chemotherapeutic resistance in cancers. The key role of the c-MET in bone metastasis as well as therapeutic resistance has been elaborated. Also, suppressive effect of selected natural compounds on the c-MET pathway in clinical/preclinical studies has been discussed.
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Affiliation(s)
- Chakrabhavi Dhananjaya Mohan
- FEST Division, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226 001, India
| | - Muthu K Shanmugam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | | | - Arunachalam Chinnathambi
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Kanchugarakoppal S Rangappa
- Institution of Excellence, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore, Karnataka 570006, India.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
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He B, Kang S, Su R, Wu S, Liu X, Liu M, Chen S. Chemoprophylaxis Effect of EGCG on the Recurrence of Colorectal Cancer: A Systematic Review and Meta-Analysis. Curr Pharm Des 2024; 30:2643-2651. [PMID: 38988171 DOI: 10.2174/0113816128319678240612114820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 05/26/2024] [Accepted: 05/29/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND AND AIMS The recurrence rate of Colorectal Cancer (CRC) after cure is always high. The purpose of this study was to investigate whether green tea extract (-)-Epigallocatechin gallate (EGCG) has an effective preventive effect on the recurrence of CRC. METHODS We conducted a systematic literature review and meta-analysis of the effects of taking EGCG or placebo on disease recurrence in patients after colon polyp removal. RESULTS Five Randomized Controlled Trials (RCTs) were included in this review. A double-blind drug trial involving 1389 participants involved EGCG and placebo. The results showed no significant publication bias or heterogeneity in the five studies (I2 = 38%; p = 0.17). Patients taking EGCG had a lower recurrence rate of CRC than those in the placebo group. The results were statistically significant (Z=2.83, p < 0.05). CONCLUSION This study demonstrated that long-term EGCG can prevent CRC recurrence to a certain extent.
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Affiliation(s)
- Benyu He
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Shuhui Kang
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Runze Su
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Sha Wu
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Xue Liu
- School of Nursing, Hebei University, Baoding, China
| | - Maosheng Liu
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Si Chen
- Zunyi Medical University, Zhuhai Campus, Zhuhai, China
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Novoa Díaz MB, Carriere P, Gigola G, Zwenger AO, Calvo N, Gentili C. Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide. World J Gastroenterol 2022; 28:3177-3200. [PMID: 36051345 PMCID: PMC9331538 DOI: 10.3748/wjg.v28.i26.3177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/21/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Parathyroid hormone-related peptide (PTHrP) plays a key role in the development and progression of many tumors. We found that in colorectal cancer (CRC) HCT116 cells, the binding of PTHrP to its receptor PTHR type 1 (PTHR1) activates events associated with an aggressive phenotype. In HCT116 cell xenografts, PTHrP modulates the expression of molecular markers linked to tumor progression. Empirical evidence suggests that the Met receptor is involved in the development and evolution of CRC. Based on these data, we hypothesized that the signaling pathway trigged by PTHrP could be involved in the transactivation of Met and consequently in the aggressive behavior of CRC cells.
AIM To elucidate the relationship among PTHR1, PTHrP, and Met in CRC models.
METHODS For in vitro assays, HCT116 and Caco-2 cells derived from human CRC were incubated in the absence or presence of PTHrP (1-34) (10-8 M). Where indicated, cells were pre-incubated with specific kinase inhibitors or dimethylsulfoxide, the vehicle of the inhibitors. The protein levels were evaluated by Western blot technique. Real-time polymerase chain reaction (RT-qPCR) was carried out to determine the changes in gene expression. Wound healing assay and morphological monitoring were performed to evaluate cell migration and changes related to the epithelial-mesenchymal transition (EMT), respectively. The number of viable HCT116 cells was counted by trypan blue dye exclusion test to evaluate the effects of irinotecan (CPT-11), oxaliplatin (OXA), or doxorubicin (DOXO) with or without PTHrP. For in vivo tests, HCT116 cell xenografts on 6-wk-old male N:NIH (S)_nu mice received daily intratumoral injections of PTHrP (40 μg/kg) in 100 μL phosphate-buffered saline (PBS) or the vehicle (PBS) as a control during 20 d. Humanitarian slaughter was carried out and the tumors were removed, weighed, and fixed in a 4% formaldehyde solution for subsequent treatment by immunoassays. To evaluate the expression of molecular markers in human tumor samples, we studied 23 specimens obtained from CRC patients which were treated at the Hospital Interzonal de Graves y Agudos Dr. José Penna (Bahía Blanca, Buenos Aires, Argentina) and the Hospital Provincial de Neuquén (Neuquén, Neuquén, Argentina) from January 1990 to December 2007. Seven cases with normal colorectal tissues were assigned to the control group. Tumor tissue samples and clinical histories of patients were analyzed. Paraffin-embedded blocks from primary tumors were reviewed by hematoxylin-eosin staining technique; subsequently, representative histological samples were selected from each patient. From each paraffin block, tumor sections were stained for immunohistochemical detection. The statistical significance of differences was analyzed using proper statistical analysis. The results were considered statistically significant at P < 0.05.
RESULTS By Western blot analysis and using total Met antibody, we found that PTHrP regulated Met expression in HCT116 cells but not in Caco-2 cells. In HCT116 cells, Met protein levels increased at 30 min (P < 0.01) and at 20 h (P < 0.01) whereas the levels diminished at 3 min (P < 0.05), 10 min (P < 0.01), and 1 h to 5 h (P < 0.01) of PTHrP treatment. Using an active Met antibody, we found that where the protein levels of total Met decreased (3 min, 10 min, and 60 min of PTHrP exposure), the status of phosphorylated/activated Met increased (P < 0.01) at the same time, suggesting that Met undergoes proteasomal degradation after its phosphorylation/activation by PTHrP. The increment of its protein level after these decreases (at 30 min and 20 h) suggests a modulation of Met expression by PTHrP in order to improve Met levels and this idea is supported by our observation that the cytokine increased Met mRNA levels at least at 15 min in HCT116 cells as revealed by RT-qPCR analysis (P < 0.05). We then proceeded to evaluate the signaling pathways that mediate the phosphorylation/ activation of Met induced by PTHrP in HCT116 cells. By Western blot technique, we observed that PP1, a specific inhibitor of the activation of the proto-oncogene protein tyrosine kinase Src, blocked the effect of PTHrP on Met phosphorylation (P < 0.05). Furthermore, the selective inhibition of the ERK 1/2 mitogen-activated protein kinase (ERK 1/2 MAPK) using PD98059 and the p38 MAPK using SB203580 diminished the effect of PTHrP on Met phosphorylation/activation (P < 0.05). Using SU11274, the specific inhibitor of Met activation, and trypan blue dye exclusion test, Western blot, wound healing assay, and morphological analysis with a microscope, we observed the reversal of cell events induced by PTHrP such as cell proliferation (P < 0.05), migration (P < 0.05), and the EMT program (P < 0.01) in HCT116 cells. Also, PTHrP favored the chemoresistance to CPT-11 (P < 0.001), OXA (P < 0.01), and DOXO (P < 0.01) through the Met pathway. Taken together, these findings suggest that Met activated by PTHrP participates in events associated with the aggressive phenotype of CRC cells. By immunohistochemical analysis, we found that PTHrP in HCT116 cell xenografts enhanced the protein expression of Met (0.190 ± 0.014) compared to tumors from control mice (0.110 ± 0.012; P < 0.05) and of its own receptor (2.27 ± 0.20) compared to tumors from control mice (1.98 ± 0.14; P < 0.01). Finally, assuming that the changes in the expression of PTHrP and its receptor are directly correlated, we investigated the expression of both Met and PTHR1 in biopsies of CRC patients by immunohistochemical analysis. Comparing histologically differentiated tumors with respect to those less differentiated, we found that the labeling intensity for Met and PTHR1 increased and diminished in a gradual manner, respectively (P < 0.05).
CONCLUSION PTHrP acts through the Met pathway in CRC cells and regulates Met expression in a CRC animal model. More basic and clinical studies are needed to further evaluate the PTHrP/Met relationship.
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Affiliation(s)
- María Belén Novoa Díaz
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Pedro Carriere
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Graciela Gigola
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | | | - Natalia Calvo
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Claudia Gentili
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
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Chen YS, Li J, Menon R, Jayaraman A, Lee K, Huang Y, Dashwood WM, Zhang K, Sun D, Dashwood RH. Dietary spinach reshapes the gut microbiome in an Apc-mutant genetic background: mechanistic insights from integrated multi-omics. Gut Microbes 2022; 13:1972756. [PMID: 34494932 PMCID: PMC8437542 DOI: 10.1080/19490976.2021.1972756] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Complex interrelationships govern the dynamic interactions between gut microbes, the host, and exogenous drivers of disease outcome. A multi-omics approach to cancer prevention by spinach (SPI) was pursued for the first time in the polyposis in rat colon (Pirc) model. SPI fed for 26 weeks (10% w/w, freeze-dried in the diet) exhibited significant antitumor efficacy and, in the Apc-mutant genetic background, β-catenin remained highly overexpressed in adenomatous polyps. However, in both wild type and Apc-mutant rats, increased gut microbiome diversity after SPI consumption coincided with reversal of taxonomic composition. Metagenomic prediction implicated linoleate and butanoate metabolism, tricarboxylic acid cycle, and pathways in cancer, which was supported by transcriptomic and metabolomic analyses. Thus, tumor suppression by SPI involved marked reshaping of the gut microbiome along with changes in host RNA-miRNA networks. When colon polyps were compared with matched normal-looking tissues via metabolomics, anticancer outcomes were linked to SPI-derived linoleate bioactives with known anti-inflammatory/ proapoptotic mechanisms, as well as N-aceto-2-hydroxybutanoate, consistent with altered butanoate metabolism stemming from increased α-diversity of the gut microbiome. In colon tumors from SPI-fed rats, L-glutamate and N-acetylneuraminate also were reduced, implicating altered mitochondrial energetics and cell surface glycans involved in oncogenic signaling networks and immune evasion. In conclusion, a multi-omics approach to cancer prevention by SPI provided mechanistic support for linoleate and butanoate metabolism, as well as tumor-associated changes in L-glutamate and N-acetylneuraminate. Additional factors, such as the fiber content, also warrant further investigation with a view to delaying colectomy and drug intervention in at-risk patients.
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Affiliation(s)
| | - Jia Li
- Texas A&M Health, Houston, USA
| | - Rani Menon
- Department of Chemical Engineering, College of Engineering, Texas A&M University, College Station, USA
| | - Arul Jayaraman
- Department of Chemical Engineering, College of Engineering, Texas A&M University, College Station, USA
| | - Kyongbum Lee
- Department of Chemical and Biological Engineering, Tufts University, Medford, USA
| | | | | | | | | | - Roderick H. Dashwood
- Texas A&M Health, Houston, USA,Department of Translational Medical Sciences, Texas A&M College of Medicine, Houston, USA,CONTACT Roderick H. Dashwood Center for Epigenetics & Disease Prevention, Texas A&M Health, Houston, 2121 W. Holcombe Blvd., Houston, Texass 77030, USA
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Kubczak M, Szustka A, Rogalińska M. Molecular Targets of Natural Compounds with Anti-Cancer Properties. Int J Mol Sci 2021; 22:ijms222413659. [PMID: 34948455 PMCID: PMC8708931 DOI: 10.3390/ijms222413659] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer is the second leading cause of death in humans. Despite rapid developments in diagnostic methods and therapies, metastasis and resistance to administrated drugs are the main obstacles to successful treatment. Therefore, the main challenge should be the diagnosis and design of optimal therapeutic strategies for patients to increase their chances of responding positively to treatment and increase their life expectancy. In many types of cancer, a deregulation of multiple pathways has been found. This includes disturbances in cellular metabolism, cell cycle, apoptosis, angiogenesis, or epigenetic modifications. Additionally, signals received from the microenvironment may significantly contribute to cancer development. Chemical agents obtained from natural sources seem to be very attractive alternatives to synthetic compounds. They can exhibit similar anti-cancer potential, usually with reduced side effects. It was reported that natural compounds obtained from fruits and vegetables, e.g., polyphenols, flavonoids, stilbenes, carotenoids and acetogenins, might be effective against cancer cells in vitro and in vivo. Several published results indicate the activity of natural compounds on protein expression by its influence on transcription factors. They could also be involved in alterations in cellular response, cell signaling and epigenetic modifications. Such natural components could be used in our diet for anti-cancer protection. In this review, the activities of natural compounds, including anti-cancer properties, are described. The influence of natural agents on cancer cell metabolism, proliferation, signal transduction and epigenetic modifications is highlighted.
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Affiliation(s)
- Małgorzata Kubczak
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Aleksandra Szustka
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Małgorzata Rogalińska
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Correspondence:
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Das A, Haque I, Ray P, Ghosh A, Dutta D, Quadir M, De A, Gunewardena S, Chatterjee I, Banerjee S, Weir S, Banerjee SK. CCN5 activation by free or encapsulated EGCG is required to render triple-negative breast cancer cell viability and tumor progression. Pharmacol Res Perspect 2021; 9:e00753. [PMID: 33745223 PMCID: PMC7981588 DOI: 10.1002/prp2.753] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 12/11/2022] Open
Abstract
Epigallocatechin-3-gallate (EGCG) has been considered an anticancer agent despite conflicting and discrepant bioavailability views. EGCG impairs the viability and self-renewal capacity of triple-negative breast cancer (TNBC) cells and makes them sensitive to estrogen via activating ER-α. Surprisingly, the mechanism of EGCG's action on TNBC cells remains unclear. CCN5/WISP-2 is a gatekeeper gene that regulates viability, ER-α, and stemness in TNBC and other types of cancers. This study aimed to investigate whether EGCG (free or encapsulated in nanoparticles) interacts with the CCN5 protein by emphasizing its bioavailability and enhancing its anticancer effect. We demonstrate that EGCG activates CCN5 to inhibit in vitro cell viability through apoptosis, the sphere-forming ability via reversing TNBC cells' stemness, and suppressing tumor growth in vivo. Moreover, we found EGCG-loaded nanoparticles to be functionally more active and superior in their tumor-suppressing ability than free-EGCG. Together, these studies identify EGCG (free or encapsulated) as a novel activator of CCN5 in TNBC cells and hold promise as a future therapeutic option for TNBC with upregulated CCN5 expression.
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Affiliation(s)
- Amlan Das
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Present address:
National Institute of Biomedical GenomicsKalyaniWest BengalIndia
| | - Inamul Haque
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
| | - Priyanka Ray
- Department of Chemical Biochemical Environmental Engineering (CBEEUniversity of MarylandBaltimoreMDUSA
| | - Arnab Ghosh
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Debasmita Dutta
- Department of Coatings and Polymeric MaterialsNorth Dakota State UniversityFargoNDUSA
| | - Mohiuddin Quadir
- Department of Coatings and Polymeric MaterialsNorth Dakota State UniversityFargoNDUSA
| | - Archana De
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
| | - Sumedha Gunewardena
- Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Indranil Chatterjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Present address:
Department of Life SciencesCentral University of Tamil NaduThiruvarurIndia
| | - Snigdha Banerjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Scott Weir
- Department of PharmacologyToxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Sushanta K. Banerjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
- Lead contact, SKB, Cancer Research UnitKansas CityMOUSA
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Ulusan AM, Rajendran P, Dashwood WM, Yavuz OF, Kapoor S, Gustafson TA, Savage MI, Brown PH, Sei S, Mohammed A, Vilar E, Dashwood RH. Optimization of Erlotinib Plus Sulindac Dosing Regimens for Intestinal Cancer Prevention in an Apc-Mutant Model of Familial Adenomatous Polyposis (FAP). Cancer Prev Res (Phila) 2021; 14:325-336. [PMID: 33277315 PMCID: PMC8137519 DOI: 10.1158/1940-6207.capr-20-0262] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 09/29/2020] [Accepted: 11/19/2020] [Indexed: 01/15/2023]
Abstract
A clinical trial in patients with familial adenomatous polyposis (FAP) demonstrated that sulindac plus erlotinib (SUL+ERL) had good efficacy in the duodenum and colon, but toxicity issues raised concerns for long-term prevention. We performed a biomarker study in the polyposis in rat colon (Pirc) model, observing phosphorylated Erk inhibition in colon polyps for up to 10 days after discontinuing ERL+SUL administration. In a follow-up study lasting 16 weeks, significant reduction of colon and small intestine (SI) tumor burden was detected, especially in rats given 250 ppm SUL in the diet plus once-a-week intragastric dosing of ERL at 21 or 42 mg/kg body weight (BW). A long-term study further demonstrated antitumor efficacy in the colon and SI at 52 weeks, when 250 ppm SUL was combined with once-a-week intragastric administration of ERL at 10, 21, or 42 mg/kg BW. Tumor-associated matrix metalloproteinase-7 (Mmp7), tumor necrosis factor (Tnf), and early growth response 1 (Egr1) were decreased at 16 weeks by ERL+SUL, and this was sustained in the long-term study for Mmp7 and Tnf. Based on the collective results, the optimal dose combination of ERL 10 mg/kg BW plus 250 ppm SUL lacked toxicity, inhibited molecular biomarkers, and exhibited effective antitumor activity. We conclude that switching from continuous to once-per-week ERL, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care SUL against adenomatous polyps in the colon and SI, with clinical relevance for patients with FAP before or after colectomy. PREVENTION RELEVANCE: This investigation concludes that switching from continuous to once-per-week erlotinib, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care sulindac against adenomatous polyps in the colon and small intestine, with clinical relevance for patients with FAP before or after colectomy.
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Affiliation(s)
- Ahmet M Ulusan
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas
- Internal Medicine, Hackensack University Medical Center, Hackensack, New Jersey
| | - Praveen Rajendran
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas.
| | - Wan Mohaiza Dashwood
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas
| | - Omer F Yavuz
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas
| | - Sabeeta Kapoor
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas
| | - Trace A Gustafson
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas
| | - Michelle I Savage
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Powel H Brown
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Shizuko Sei
- Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland
| | - Altaf Mohammed
- Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland
| | - Eduardo Vilar
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
| | - Roderick H Dashwood
- Center for Epigenetics and Disease Prevention, Texas A&M Health Science Center, Houston, Texas.
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Pharmacological Potential and Chemical Characterization of Bridelia ferruginea Benth.-A Native Tropical African Medicinal Plant. Antibiotics (Basel) 2021; 10:antibiotics10020223. [PMID: 33672329 PMCID: PMC7926895 DOI: 10.3390/antibiotics10020223] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 02/19/2021] [Accepted: 02/20/2021] [Indexed: 12/19/2022] Open
Abstract
To avail the possible pharmacological actions of Brideliaferruginea Benth., the present investigation was designed to quantitatively analyze the total flavonoid and phenolic contents and assess the various antioxidant and enzyme inhibition properties of leaf and stem bark extracts (ethyl acetate, water and methanolic) of B. ferruginea. Anti-proliferative effect was also investigated against human colon cancer cells (HCT116) as well as the antimicrobial potential against multiple bacterial and fungal (yeasts and dermatophytes) strains. The methanolic and water extracts of the stem bark demonstrated the highest phenolic content (193.58 ± 0.98 and 187.84 ± 1.88 mg/g, respectively), while the leaf extracts showed comparatively higher flavonoid contents (24.37-42.31 mg/g). Overall, the methanolic extracts were found to possess the most significant antioxidant potency. Compared to the other extracts, methanolic extracts of the B. ferruginea were revealed to be most potent inhibitors of acetyl- and butyryl-cholinesterases, tyrosinase α-amylase, except α-glucosidase. Only the ethyl acetate extracts were found to inhibit glucosidase. Additionally, the stem bark methanolic extract also showed potent inhibitory activity against E. coli and gram-positive bacteria (MIC (minimum inhibitory concentration): 2.48-62.99 µg/mL), as well as all the tested fungi (MIC: 4.96-62.99 µg/mL). In conclusion, B. ferruginea can be regarded as a promising source of bioactive compounds displaying multifunctional pharmacological activities and thus is a potential candidate for further investigations in the endeavor to develop botanical formulations for pharmaceutical and cosmeceutical industries.
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Villota H, Röthlisberger S, Pedroza-Díaz J. Modulation of the Canonical Wnt Signaling Pathway by Dietary Polyphenols, an Opportunity for Colorectal Cancer Chemoprevention and Treatment. Nutr Cancer 2021; 74:384-404. [PMID: 33596716 DOI: 10.1080/01635581.2021.1884730] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last few decades there has been a rise in the worldwide incidence of colorectal cancer which can be traced back to the influence of well-known modifiable risk factors such as lifestyle, diet and obesity. Conversely, the consumption of fruits, vegetables and fiber decreases the risk of CRC, which is why dietary polyphenols have aroused interest in recent years as potentially anti-carcinogenic compounds. One of the driving forces of colorectal carcinogenesis, in both sporadic and hereditary CRC, is the aberrant activation/regulation of the Wnt/β-catenin pathway. This review discusses reports of modulation of the Wnt/β-Catenin signaling pathway by dietary polyphenols (resveratrol, avenanthramides, epigallocatechinin, curcumin, quercetin, silibinin, genistein and mangiferin) specifically focusing on CRC, and proposes a model as to how this modulation occurs. There is potential for implementing these dietary polyphenols into preventative and therapeutic therapies for CRC as evidenced by some clinical trials that have been carried out with promising results.
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Affiliation(s)
- Hernan Villota
- Biomedical Innovation and Research Group, Faculty of Applied and Exact Sciences, Instituto Tecnologico Metropolitano, Medellin, Colombia
| | - Sarah Röthlisberger
- Biomedical Innovation and Research Group, Faculty of Applied and Exact Sciences, Instituto Tecnologico Metropolitano, Medellin, Colombia
| | - Johanna Pedroza-Díaz
- Biomedical Innovation and Research Group, Faculty of Applied and Exact Sciences, Instituto Tecnologico Metropolitano, Medellin, Colombia
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10
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Ciesielski O, Biesiekierska M, Balcerczyk A. Epigallocatechin-3-gallate (EGCG) Alters Histone Acetylation and Methylation and Impacts Chromatin Architecture Profile in Human Endothelial Cells. Molecules 2020; 25:molecules25102326. [PMID: 32429384 PMCID: PMC7287656 DOI: 10.3390/molecules25102326] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/13/2020] [Accepted: 05/14/2020] [Indexed: 01/07/2023] Open
Abstract
Epigallocatechin gallate (EGCG), the main green tea polyphenol, exerts a wide variety of biological actions. Epigenetically, the catechin has been classified as a DNMTs inhibitor, however, its impact on histone modifications and chromatin structure is still poorly understood. The purpose of this study was to find the impact of EGCG on the histone posttranslational modifications machinery and chromatin remodeling in human endothelial cells of both microvascular (HMEC-1) and vein (HUVECs) origin. We analyzed the methylation and acetylation status of histones (Western blotting), as well as assessed the activity (fluorometric assay kit) and gene expression (qPCR) of the enzymes playing a prominent role in shaping the human epigenome. The performed analyses showed that EGCG increases histone acetylation (H3K9/14ac, H3ac), and methylation of both active (H3K4me3) and repressive (H3K9me3) chromatin marks. We also found that the catechin acts as an HDAC inhibitor in cellular and cell-free models. Additionally, we observed that EGCG affects chromatin architecture by reducing the expression of heterochromatin binding proteins: HP1α, HP1γ. Our results indicate that EGCG promotes chromatin relaxation in human endothelial cells and presents a broad epigenetic potential affecting expression and activity of epigenome modulators including HDAC5 and 7, p300, CREBP, LSD1 or KMT2A.
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Affiliation(s)
- Oskar Ciesielski
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; (O.C.); (M.B.)
- The Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, University of Łódź, Banacha 12/16, 90-237 Lodz, Poland
| | - Marta Biesiekierska
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; (O.C.); (M.B.)
| | - Aneta Balcerczyk
- Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; (O.C.); (M.B.)
- Correspondence: ; Tel.: +48-42-635-45-10
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11
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Wang ST, Cui WQ, Pan D, Jiang M, Chang B, Sang LX. Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer. World J Gastroenterol 2020; 26:562-597. [PMID: 32103869 PMCID: PMC7029350 DOI: 10.3748/wjg.v26.i6.562] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/30/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/β-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.
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Affiliation(s)
- Shi-Tong Wang
- Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wen-Qi Cui
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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12
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Chen J, Zhang L, Li C, Chen R, Liu C, Chen M. Lipophilized Epigallocatechin Gallate Derivative Exerts Anti-Proliferation Efficacy through Induction of Cell Cycle Arrest and Apoptosis on DU145 Human Prostate Cancer Cells. Nutrients 2019; 12:E92. [PMID: 31905647 PMCID: PMC7020104 DOI: 10.3390/nu12010092] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 12/16/2019] [Accepted: 12/25/2019] [Indexed: 11/16/2022] Open
Abstract
Epigallocatechin gallate (EGCG) is the predominant tea polyphenol and it exhibits a hydrophilic character. The lipophilized EGCG derivative (LEGCG) was synthesized by enzymatic esterification of EGCG with lauric acid to enhance its bioactivity. The tetralauroyl EGCG was confirmed by high-performance liquid chromatography-tandem mass spectrometry and further identified as 3', 5', 3″, 5″-4-O-lauroyl EGCG by 1H and 13C nuclear magnetic resonance. The anti-proliferation effect of LEGCG on DU145 human prostate carcinoma cells was evaluated by MTT assay. In addition, the underlying molecular mechanism by which LEGCG exerts anti-proliferation efficacy was elucidated by flow cytometry and immunoblot analysis. Results suggested that LEGCG exhibited a dose-dependent anti-proliferation effect on DU145 cells by G0/G1 phase arrest and induction of apoptosis. LEGCG induced cell cycle arrest via p53/p21 activation, which down-regulated the cyclin D1 and CDK4 expression. In addition, LEGCG induced apoptosis by increasing the Bax/Bcl-2 ratio, the cytochrome c release, and the caspases cleavage on DU145 cells. The results provide theoretical support to prevent prostate cancer with LEGCG.
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Affiliation(s)
| | | | | | | | | | - Mingshun Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
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13
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Liu C, Li P, Qu Z, Xiong W, Liu A, Zhang S. Advances in the Antagonism of Epigallocatechin-3-gallate in the Treatment of Digestive Tract Tumors. Molecules 2019; 24:molecules24091726. [PMID: 31058847 PMCID: PMC6539113 DOI: 10.3390/molecules24091726] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 04/24/2019] [Accepted: 04/30/2019] [Indexed: 12/12/2022] Open
Abstract
Due to changes in the dietary structure of individuals, the incidence of digestive tract tumors has increased significantly in recent years, causing a serious threat to the life and health of patients. This has in turn led to an increase in cancer prevention research. Many studies have shown that epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, is in direct contact with the digestive tract upon ingestion, which allows it to elicit a significant antagonizing effect on digestive tract tumors. The main results of EGCG treatment include the prevention of tumor development in the digestive tract and the induction of cell cycle arrest and apoptosis. EGCG can be orally administered, is safe, and combats other resistances. The synergistic use of cancer drugs can promote the efficacy and reduce the anti-allergic properties of drugs, and is thus, favored in medical research. EGCG, however, currently possesses several shortcomings such as poor stability and low bioavailability, and its clinical application prospects need further development. In this paper, we have systematically summarized the research progress on the ability of EGCG to antagonize the activity and mechanism of action of digestive tract tumors, to achieve prevention, alleviation, delay, and even treat human gastrointestinal tract tumors via exogenous dietary EGCG supplementation or the development of new drugs containing EGCG.
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Affiliation(s)
- Changwei Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Penghui Li
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Zhihao Qu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Wei Xiong
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha 410078, China.
| | - Ailing Liu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.
| | - Sheng Zhang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
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14
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Encapsulation of EGCG and esterified EGCG derivatives in double emulsions containing Whey Protein Isolate, Bacterial Cellulose and salt. Food Chem 2019; 281:171-177. [DOI: 10.1016/j.foodchem.2018.12.105] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 12/20/2018] [Accepted: 12/21/2018] [Indexed: 01/08/2023]
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15
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Rady I, Mohamed H, Rady M, Siddiqui IA, Mukhtar H. Cancer preventive and therapeutic effects of EGCG, the major polyphenol in green tea. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.ejbas.2017.12.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Islam Rady
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
- Department of Zoology, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Hadir Mohamed
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
| | - Mohamad Rady
- Department of Zoology, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Imtiaz A. Siddiqui
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
| | - Hasan Mukhtar
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
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16
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Zhao Y, Hu X, Zuo X, Wang M. Chemopreventive effects of some popular phytochemicals on human colon cancer: a review. Food Funct 2018; 9:4548-4568. [DOI: 10.1039/c8fo00850g] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The present review summarizes (1) the epidemiology and etiology of colon cancer, (2) generalized cancer chemoprotective mechanisms, and (3) the chemopreventive properties of some popular phytochemicals as well as some phytochemicals developed by our research group recently.
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Affiliation(s)
- Yueliang Zhao
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
| | - Xiaoqian Hu
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
| | - Xinyuan Zuo
- School of Petroleum and Chemical Engineering
- Dalian University of Technology
- Panjin City
- China
| | - Mingfu Wang
- College of Food Science and Technology
- Shanghai Ocean University
- Shanghai
- China
- Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai)
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17
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Kelso TWR, Porter DK, Amaral ML, Shokhirev MN, Benner C, Hargreaves DC. Chromatin accessibility underlies synthetic lethality of SWI/SNF subunits in ARID1A-mutant cancers. eLife 2017; 6:30506. [PMID: 28967863 PMCID: PMC5643100 DOI: 10.7554/elife.30506] [Citation(s) in RCA: 132] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 09/28/2017] [Indexed: 02/06/2023] Open
Abstract
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here, we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation. Changes in accessibility are predictive of changes in expression and correlate with loss of H3K4me and H3K27ac marks, nucleosome spacing, and transcription factor binding, particularly at growth pathway genes including MET. We find that ARID1B knockdown in ARID1A mutant ovarian cancer cells causes similar loss of enhancer architecture, suggesting that this is a conserved function underlying the synthetic lethality between ARID1A and ARID1B.
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Affiliation(s)
- Timothy W R Kelso
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, California, United States
| | - Devin K Porter
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, California, United States
| | - Maria Luisa Amaral
- The Razavi Newman Integrative Genomics and Bioinformatics Core Facility, Salk Institute for Biological Studies, California, United States
| | - Maxim N Shokhirev
- The Razavi Newman Integrative Genomics and Bioinformatics Core Facility, Salk Institute for Biological Studies, California, United States
| | - Christopher Benner
- Department of Medicine, University of California San Diego, California, United States
| | - Diana C Hargreaves
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, California, United States
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18
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Gómez-Mascaraque LG, Hernández-Rojas M, Tarancón P, Tenon M, Feuillère N, Vélez Ruiz JF, Fiszman S, López-Rubio A. Impact of microencapsulation within electrosprayed proteins on the formulation of green tea extract-enriched biscuits. Lebensm Wiss Technol 2017. [DOI: 10.1016/j.lwt.2017.03.041] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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19
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Falcó I, Randazzo W, Gómez-Mascaraque L, Aznar R, López-Rubio A, Sánchez G. Effect of (−)-epigallocatechin gallate at different pH conditions on enteric viruses. Lebensm Wiss Technol 2017. [DOI: 10.1016/j.lwt.2017.03.050] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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20
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Gan RY, Li HB, Sui ZQ, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr 2017. [DOI: 10.1080/10408398.2016.1231168 pmid: 27645804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Affiliation(s)
- Ren-You Gan
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- School of Biological Sciences, The University of Hong Kong, Hong Kong
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Zhong-Quan Sui
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Harold Corke
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- School of Biological Sciences, The University of Hong Kong, Hong Kong
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21
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Gan RY, Li HB, Sui ZQ, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr 2017; 58:924-941. [PMID: 27645804 DOI: 10.1080/10408398.2016.1231168] [Citation(s) in RCA: 287] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.
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Affiliation(s)
- Ren-You Gan
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China.,b School of Biological Sciences , The University of Hong Kong , Hong Kong
| | - Hua-Bin Li
- c Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition , School of Public Health, Sun Yat-Sen University , Guangzhou , China
| | - Zhong-Quan Sui
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China
| | - Harold Corke
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China.,b School of Biological Sciences , The University of Hong Kong , Hong Kong
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22
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Gómez-Mascaraque LG, Soler C, Lopez-Rubio A. Stability and bioaccessibility of EGCG within edible micro-hydrogels. Chitosan vs. gelatin, a comparative study. Food Hydrocoll 2016. [DOI: 10.1016/j.foodhyd.2016.05.009] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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23
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Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin Cancer Biol 2016; 40-41:35-47. [DOI: 10.1016/j.semcancer.2016.03.005] [Citation(s) in RCA: 171] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Revised: 03/29/2016] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
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24
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Impact of molecular weight on the formation of electrosprayed chitosan microcapsules as delivery vehicles for bioactive compounds. Carbohydr Polym 2016; 150:121-30. [DOI: 10.1016/j.carbpol.2016.05.012] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 05/02/2016] [Accepted: 05/05/2016] [Indexed: 12/12/2022]
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25
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Kim H, Banerjee N, Ivanov I, Pfent CM, Prudhomme KR, Bisson WH, Dashwood RH, Talcott ST, Mertens-Talcott SU. Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis. Mol Nutr Food Res 2016; 60:1912-23. [PMID: 27028006 DOI: 10.1002/mnfr.201501008] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 03/15/2016] [Accepted: 03/17/2016] [Indexed: 12/12/2022]
Abstract
SCOPE Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. METHODS AND RESULTS In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. CONCLUSION Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis.
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Affiliation(s)
- Hyemee Kim
- Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA
| | - Nivedita Banerjee
- Interdisciplinary Program of Toxicology, Texas A&M University, College Station, TX, USA
| | - Ivan Ivanov
- Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA
| | - Catherine M Pfent
- Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA
| | - Kalan R Prudhomme
- Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA
| | - William H Bisson
- Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA
| | - Roderick H Dashwood
- Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA.,Center for Epigenetics & Disease Prevention, Texas A&M Health Science Center, Houston, TX, USA
| | - Stephen T Talcott
- Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA
| | - Susanne U Mertens-Talcott
- Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA. .,Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
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26
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Ahmed RSI, Liu G, Renzetti A, Farshi P, Yang H, Soave C, Saed G, El-Ghoneimy AA, El-Banna HA, Foldes R, Chan TH, Dou QP. Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines. J Cell Biochem 2016; 117:2357-69. [DOI: 10.1002/jcb.25533] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 03/03/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Reda Saber Ibrahim Ahmed
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
- Faculty of Veterinary Medicine, Department of Pharmacology; South Valley University; Qena Egypt
| | - Gang Liu
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
| | - Andrea Renzetti
- Department of Chemistry; McGill University; Montreal Quebec Canada
| | - Pershang Farshi
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
| | - Huanjie Yang
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
| | - Claire Soave
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
| | - Ghassan Saed
- Departments of Obstetrics & Gynecology and Anatomy & Cell Biology; School of Medicine; Wayne State University; Detroit Michigan
| | | | - Hossny Awad El-Banna
- Faculty of Veterinary Medicine, Department of Pharmacology; Cairo University; Giza Egypt
| | - Robert Foldes
- Viteava Pharmaceuticals Inc.; Toronto Ontario Canada
| | - Tak-Hang Chan
- Department of Chemistry; McGill University; Montreal Quebec Canada
| | - Q. Ping Dou
- Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine; Wayne State University; Detroit Michigan
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Zhou Q, Bennett LL, Zhou S. Multifaceted ability of naturally occurring polyphenols against metastatic cancer. Clin Exp Pharmacol Physiol 2016; 43:394-409. [DOI: 10.1111/1440-1681.12546] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 01/07/2016] [Accepted: 01/08/2016] [Indexed: 02/01/2023]
Affiliation(s)
- Qingyu Zhou
- Department of Pharmaceutical Sciences; College of Pharmacy; University of South Florida; Tampa Florida
| | | | - Shufeng Zhou
- Department of Pharmaceutical Sciences; College of Pharmacy; University of South Florida; Tampa Florida
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Gómez-Mascaraque LG, Lagarón JM, López-Rubio A. Electrosprayed gelatin submicroparticles as edible carriers for the encapsulation of polyphenols of interest in functional foods. Food Hydrocoll 2015. [DOI: 10.1016/j.foodhyd.2015.03.006] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
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Zhu S, Li Y, Li Z, Ma C, Lou Z, Yokoyama W, Wang H. Lipase-catalyzed synthesis of acetylated EGCG and antioxidant properties of the acetylated derivatives. Food Res Int 2014. [DOI: 10.1016/j.foodres.2013.10.026] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
Many studies suggest that Western lifestyle and dietary factors may be responsible for the high incidence of colorectal cancer in industrialized countries. Consumption of high amounts of red and processed meat and low intake of fiber and multiple protective phytochemicals found in fruits, vegetables, and whole grains might be responsible for the high incidence of this neoplasm in the Western world. Additionally, obesity, lack of physical activity, tobacco and alcohol use, sleep deprivation, and other factors have been proven to further increase the risk of colorectal cancer. Identifying and understanding the mechanisms through which they impact colon carcinogenesis is needed for the introduction of protective lifestyle recommendations.
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Affiliation(s)
- Lukasz Durko
- Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland
| | - Ewa Malecka-Panas
- Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland
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Optimization of lipase-catalyzed synthesis of acetylated EGCG by response surface methodology. ACTA ACUST UNITED AC 2013. [DOI: 10.1016/j.molcatb.2013.08.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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González-Vallinas M, González-Castejón M, Rodríguez-Casado A, Ramírez de Molina A. Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives. Nutr Rev 2013; 71:585-99. [DOI: 10.1111/nure.12051] [Citation(s) in RCA: 181] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Derry MM, Raina K, Agarwal C, Agarwal R. Identifying molecular targets of lifestyle modifications in colon cancer prevention. Front Oncol 2013; 3:119. [PMID: 23675573 PMCID: PMC3653120 DOI: 10.3389/fonc.2013.00119] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Accepted: 04/28/2013] [Indexed: 12/17/2022] Open
Abstract
One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.
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Affiliation(s)
- Molly M Derry
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus Aurora, CO, USA
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Wang H, Khor TO, Shu L, Su Z, Fuentes F, Lee JH, Kong ANT. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med Chem 2012; 12:1281-305. [PMID: 22583408 PMCID: PMC4017674 DOI: 10.2174/187152012803833026] [Citation(s) in RCA: 318] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2011] [Revised: 03/06/2012] [Accepted: 03/06/2012] [Indexed: 11/22/2022]
Abstract
Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients' cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to prevent, impede, delay, or cure cancer. This review summarizes the latest research in cancer chemoprevention and treatment using the bioactive components from natural plants. Relevant molecular mechanisms involved in the pharmacological effects of these phytochemicals are discussed. Pharmaceutical developmental challenges and opportunities in bringing the phytochemicals into the market are also explored. The authors wish to expand this research area not only for their scientific soundness, but also for their potential druggability.
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Affiliation(s)
- Hu Wang
- Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Tin Oo Khor
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Limin Shu
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Zhengyuen Su
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Francisco Fuentes
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Jong-Hun Lee
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
| | - Ah-Ng Tony Kong
- Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
- Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
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Weng CJ, Yen GC. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev 2012; 31:323-51. [DOI: 10.1007/s10555-012-9347-y] [Citation(s) in RCA: 151] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Schnekenburger M, Diederich M. Epigenetics Offer New Horizons for Colorectal Cancer Prevention. CURRENT COLORECTAL CANCER REPORTS 2012. [PMID: 22389639 DOI: 10.1007/s11888-011-0116-z116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries. Epigenetic modifications including changes in DNA methylation, histone modifications, and non-coding RNAs play a critical role in carcinogenesis. Epidemiological data suggest that, in comparison to other cancers, these alterations are particularly common within the gastrointestinal tract. To explain these observations, environmental factors and especially diet were suggested to both prevent and induce CRC. Epigenetic alterations are, in contrast to genetic modifications, potentially reversible, making the use of dietary agents a promising approach in CRC for the development of chemopreventive strategies targeting epigenetic mechanisms. This review focuses on CRC-related epigenetic alterations as a rationale for various levels of prevention strategies and their potential modulation by natural dietary compounds.
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Affiliation(s)
- Michael Schnekenburger
- Laboratoire de Biologie Moléculaire et Cellulaire de Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg
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Abstract
In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries. Epigenetic modifications including changes in DNA methylation, histone modifications, and non-coding RNAs play a critical role in carcinogenesis. Epidemiological data suggest that, in comparison to other cancers, these alterations are particularly common within the gastrointestinal tract. To explain these observations, environmental factors and especially diet were suggested to both prevent and induce CRC. Epigenetic alterations are, in contrast to genetic modifications, potentially reversible, making the use of dietary agents a promising approach in CRC for the development of chemopreventive strategies targeting epigenetic mechanisms. This review focuses on CRC-related epigenetic alterations as a rationale for various levels of prevention strategies and their potential modulation by natural dietary compounds.
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Liu Y, Shi QF, Ye YC, Tashiro SI, Onodera S, Ikejima T. Activated O2^|^bull;^|^minus; and H2O2 Mediated Cell Survival in SU11274-Treated Non-Small-Cell Lung Cancer A549 Cells via c-Met^|^ndash;PI3K^|^ndash;Akt and c-Met^|^ndash;Grb2/SOS^|^ndash;Ras^|^ndash;p38 Pathways. J Pharmacol Sci 2012; 119:150-9. [DOI: 10.1254/jphs.12048fp] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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40
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Lim YC, Cha YY. Epigallocatechin-3-gallate induces growth inhibition and apoptosis of human anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and cyclin B1/CDK1 complex. J Surg Oncol 2011; 104:776-80. [DOI: 10.1002/jso.21999] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2011] [Accepted: 05/27/2011] [Indexed: 11/09/2022]
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41
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Wang R, Dashwood RH. Endothelins and their receptors in cancer: identification of therapeutic targets. Pharmacol Res 2011; 63:519-24. [PMID: 21251982 PMCID: PMC3109221 DOI: 10.1016/j.phrs.2011.01.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2010] [Revised: 12/21/2010] [Accepted: 01/04/2011] [Indexed: 11/15/2022]
Abstract
Endothelins and their receptors are important in normal physiology, but have been implicated in various pathophysiological conditions. Members of the so-called "endothelin axis" are dysregulated in a wide range of human cancers, opening the door for novel anticancer therapies. Established cancer chemotherapeutic agents and drugs that target specific components of the endothelin axis have been combined with promising results, but more work is needed in this area. The endothelin axis affects numerous signaling pathways, including Ras, mitogen activated protein kinases, β-catenin/T-cell factor/lymphoid enhancer factor, nuclear factor-κB (NFκB), SNAIL, and mammalian target of rapamycin (mTOR). There is much still to learn about optimizing drug specificity in this area, while minimizing off-target effects. Selective agonists and antagonists of endothelins, their receptors, and upstream processing enzymes, as well as knockdown strategies in vitro, are providing valuable leads for testing in the clinical setting. The endothelin axis continues to be an attractive avenue of scientific endeavor, both in the cancer arena and in other important health-related disciplines.
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Affiliation(s)
- Rong Wang
- Linus Pauling Institute, Oregon State University, Corvallis, OR
| | - Roderick H. Dashwood
- Linus Pauling Institute, Oregon State University, Corvallis, OR
- Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR
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Shimizu M, Adachi S, Masuda M, Kozawa O, Moriwaki H. Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases. Mol Nutr Food Res 2011; 55:832-43. [PMID: 21538846 DOI: 10.1002/mnfr.201000622] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Revised: 03/17/2011] [Accepted: 03/24/2011] [Indexed: 12/14/2022]
Abstract
Recent studies indicate that receptor tyrosine kinases (RTKs), which play important roles in cell proliferation, are one of the possible targets of green tea catechins (GTCs) in cancer cell growth inhibition. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, inhibits cell proliferation and induces apoptosis in various types of cancer cells, including colorectal cancer and hepatocellular carcinoma cells, by blocking the activation of the epidermal growth factor receptor (EGFR) family of RTKs. EGCG inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R) and VEGFR2, the other members of the RTK family, and this effect is also associated with the anticancer and chemopreventive properties of this agent. EGCG suppresses the activation of EGFR in part by altering membrane lipid organization and causing the subsequent inhibition of the dimerization and activation of this receptor. Preliminary trials have shown that GTCs successfully prevent the development and progression of precancerous lesions, such as colorectal adenomas, without causing severe adverse effects. The present report reviews evidence indicating that GTCs exert anticancer and chemopreventive effects by inhibiting the activation of specific RTKs, especially EGFR, IGF-1R, and VEGFR2, and concludes that targeting RTKs and their related signaling pathways by using tea catechins could be a promising strategy for the prevention of human cancers.
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Affiliation(s)
- Masahito Shimizu
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
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Abstract
Access to a wealth of information on the internet has led many cancer patients to use complementary methods as an adjunct to traditional therapy for cancer, with, and more often, without informing their primary caregiver. Of the common complementary modalities, the use of dietary supplements appears to be highly prevalent in patients in active treatment for cancer, and later in cancer survivors. Emerging research suggests that some plant-based agents may, indeed, impact late-stage cancer, influencing molecular processes corrupted by tumor cells to evade detection, expand clonally, and invade surrounding tissues. The intent of this article is to review some of the current science underpinning the use of nutraceuticals in the latter stages of cancer.
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Pan MH, Lai CS, Wu JC, Ho CT. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Mol Nutr Food Res 2010; 55:32-45. [PMID: 21207511 DOI: 10.1002/mnfr.201000412] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 09/26/2010] [Accepted: 10/08/2010] [Indexed: 12/18/2022]
Abstract
Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action.
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Affiliation(s)
- Min-Hsiung Pan
- Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan.
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45
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Larsen CA, Dashwood RH, Bisson WH. Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights and human relevance. Pharmacol Res 2010; 62:457-64. [PMID: 20691268 PMCID: PMC2974766 DOI: 10.1016/j.phrs.2010.07.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2010] [Revised: 07/27/2010] [Accepted: 07/28/2010] [Indexed: 01/05/2023]
Abstract
Receptor tyrosine kinases (RTKs) play important roles in the control of fundamental cellular processes, influencing the balance between cell proliferation and death. RTKs have emerged as molecular targets for the treatment of various cancers. Green tea and its polyphenolic compounds, the catechins, exhibit chemopreventive and chemotherapeutic properties in many human cancer cell types, as well as in various carcinogenicity models in vivo. Epidemiological studies are somewhat less convincing, but some positive correlations have been observed. The tea catechins, including (-)-epigallocatechin-3-gallate (EGCG), have pleiotropic effects on cellular proteins and signaling pathways. This review focuses on the ability of the tea constituents to suppress RTK signaling, and summarizes the mechanisms by which EGCG and other catechins might exert their protective effects towards dysregulated RTKs in cancer cells. The findings are discussed in the context of ongoing clinical trials with RTK inhibitors, and the possibility for drug/nutrient interactions enhancing therapeutic efficacy.
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Affiliation(s)
| | - Roderick H. Dashwood
- Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
- Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA
| | - William H. Bisson
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
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46
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Wang HC, Wu DH, Chang YC, Li YJ, Wang CJ. Solanum nigrum Linn. water extract inhibits metastasis in mouse melanoma cells in vitro and in vivo. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010; 58:11913-11923. [PMID: 21028816 DOI: 10.1021/jf1022065] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Metastatic melanoma is an aggressive skin cancer notoriously resistant to current cancer therapies. Thus, new treatment strategies are urgently needed. Solanum nigrum Linn., commonly used in Oriental medicine, has showed antineoplastic activity in human cancer cell lines. The aim of this study was to evaluate the inhibitive effect of S. nigrum Linn. water extract (SNWE) on melanoma metastasis and dissect the underlying mechanisms of SNWE actions. B16-F1 cells were analyzed for migrating and invasive abilities with SNWE treatment, and several putative targets involved in metastatic melanoma were examined. In parallel, primary mouse xenograft and lung metastasis of melanoma models were established to examine the therapeutic potential of SNWE. The results indicated SNWE significantly inhibited B16-F1 cell migration and invasion. Meanwhile, decreased Akt activity and PKCα, Ras, and NF-κB protein expressions were detected in dose-dependent manners. In line with this notion, >50% reduced tumor weight and lung metastatic nodules were observed in 1% SNWE fed mice. This was associated with reduced serum MMP-9 as well as Akt activity and PKCα, Ras, and NF-κB protein expressions. Thus, this work indicates SNWE has potential application for treating metastatic melanoma.
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Affiliation(s)
- Hsueh-Chun Wang
- Institute of Biochemistry and Biotechnology, Chung Shan Medical University, and Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
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