Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.

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UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition

Journal of Clinical Medicine ◽

10.3390/jcm8040560 ◽

2019 ◽

Vol 8 (4) ◽

pp. 560 ◽

Cited By ~ 5

Author(s):

Javier Martinez-Useros ◽

Nuria Garcia-Carbonero ◽

Weiyao Li ◽

Maria J. Fernandez-Aceñero ◽

Ion Cristobal ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Epithelial To Mesenchymal Transition ◽

Rna Binding ◽

Human Colon ◽

Human Colon Cancer ◽

Mesenchymal Transition ◽

Colorectal Cancer Progression

CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.

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Synthesis, Antiproliferative Activity and Molecular Docking of New Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178617666200319114611 ◽

2020 ◽

Vol 17 (12) ◽

pp. 951-958

Author(s):

Pallava Nagaraju ◽

Pedavenkatagari Narayana Reddy ◽

Pannala Padmaja ◽

Vinod G. Ugale

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Antiproliferative Activity ◽

Aromatic Aldehydes ◽

Human Colon ◽

Docking Studies ◽

Human Colon Cancer ◽

One Pot ◽

Human Embryonic Kidney Cells ◽

Heterocyclic Molecules

A new class of 4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and 5H,6Hpyrano[ 2,3-d]thiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized via the one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one to various aromatic aldehydes and malononitrile. This domino transformation involves the formation of pyranopyrimidine ring by the formation of three C–C bonds and one C– O bond a single synthetic operation. As the products precipitate out of the reaction, simple filtration is enough to gather the products, and thus, there is no need for work-up or column-chromatography. The synthesized thiazole/benzothiazole fused pyranopyrimidine derivatives were evaluated for their antiproliferative activity against four cancer cell lines namely DU 145 (prostate cancer), Hela (Human cervical cancer), MDA-MB-231 (breast cancer), HT-29 (Human colon cancer) and normal cell line HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal cells. Among these compounds, 2-amino-9- methoxy-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidine- 3-carbonitrile 4i exhibited the most potent antiproliferative activity against the tested cell lines. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

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Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1

Cancers ◽

10.3390/cancers13133265 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3265

Author(s):

Yasuaki Kabe ◽

Ikko Koike ◽

Tatsuya Yamamoto ◽

Miwa Hirai ◽

Ayaka Kanai ◽

...

Keyword(s):

Progesterone Receptor ◽

Cancer Progression ◽

Egf Receptor ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Human Colon ◽

Titration Calorimetry ◽

Membrane Component ◽

Human Colon Cancer ◽

Receptor Membrane

Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, specifically binds to heme-dimerized PGRMC1. Binding analyses using isothermal titration calorimetry revealed that some GL derivatives, including its glucoside-derivative (GlucoGL), bind to PGRMC1 potently, whereas its aglycone, glycyrrhetinic acid (GA), does not bind. GL and GlucoGL inhibit the interaction between PGRMC1 and EGFR, thereby suppressing EGFR-mediated signaling required for cancer progression. GL and GlucoGL significantly enhanced EGFR inhibitor erlotinib- or cisplatin (CDDP)-induced cell death in human colon cancer HCT116 cells. In addition, GL derivatives suppressed the intracellular uptake of low-density lipoprotein (LDL) by inhibiting the interaction between PGRMC1 and the LDL receptor (LDLR). Effects on other pathways cannot be excluded. Treatment with GlucoGL and CDDP significantly suppressed tumor growth following xenograft transplantation in mice. Collectively, this study indicates that GL derivatives are novel inhibitors of PGRMC1 that suppress cancer progression, and our findings provide new insights for cancer treatment.

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Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.113813 ◽

2021 ◽

Vol 270 ◽

pp. 113813

Author(s):

Djabir Daddiouaissa ◽

Azura Amid ◽

Muhamad Shirwan Abdullah Sani ◽

Ahmed A.M. Elnour

Keyword(s):

Colon Cancer ◽

Ionic Liquid ◽

Cell Lines ◽

Human Colon ◽

Ht29 Cell ◽

Fruit Pulp ◽

Human Colon Cancer

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In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2005.05.093 ◽

2005 ◽

Vol 15 (17) ◽

pp. 3930-3933 ◽

Cited By ~ 92

Author(s):

Rosaria Ottanà ◽

Stefania Carotti ◽

Rosanna Maccari ◽

Ida Landini ◽

Giuseppa Chiricosta ◽

...

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Colon ◽

Colon Cancer Cell ◽

Human Colon Cancer Cell ◽

Human Colon Cancer ◽

Colon Cancer Cell Lines

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IN VITRO CYTOTOXIC ACTIVITY OF ISOLATED COMPOUNDS FROM VIBURNUM PUNCTATUM BUCH-HAM EX D. DON

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i1.16622 ◽

2016 ◽

Vol 9 (1) ◽

pp. 85

Author(s):

A. Renjith Alex ◽

K. Ilango

Keyword(s):

Cytotoxic Activity ◽

Anticancer Activity ◽

Cell Lines ◽

Methanol Extract ◽

Methanolic Extract ◽

Human Colon ◽

Human Colon Cancer ◽

Chloroform Methanol ◽

Human Colon Cancer Cells

Objective: The main aim of the study was to screen the isolated compounds of Viburnum Punctatum for its in vitro anticancer activity and its percentage viability against HCT 15 (Human Colon Cancer Cells) Cell lines.Methods: Pet ether, Chloroform, Methanol and Aqueous extracts was prepared and assayed for the presence of phytochemicals. Two compounds were isolated from the methanol extract of Viburnum Punctatum by column chromatography such as ME1 (Quercetin) and ME2 (Kaemferol-3-glycoside) characterised by UV, IR, MS, 1H NMR and 13C NMR. The above isolated compounds were subjected to in vitro anticancer activity on HCT 15 cell lines was evaluated by Micro culture Tetrazolium (MTT) assay.Results: ME1 showed significant cytotoxic activity than the ME2 on HCT 15 cells with a percentage viability of 54.60 and 67.18 in the concentration of 10µg/ml and 50µg/ml respectively.Conclusion: On the basis of obtained results, ME1 and ME2 isolated from a methanolic extract of Viburnum Punctatum represent a new group of cytotoxic against HCT 15 Cell lines.

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