Tolerance of cancer cells against amino acids deprivation in tumour microenvironments

New approaches for treating cancers are required and advances in 'omics' technologies including genomics, epigenomics, transcriptomics could provide valuable treatment options. Associate Professor Tsuyoshi Osawa, Research Center for Advanced Science and Technology (RCAST), University of Tokyo, believes that integrative techniques are essential in combating cancer. Osawa's lab is utilising a pioneering approach called nutriomics that involves applying multiple omics technologies to cancer biology. These omics approaches can be used to generate detailed genetic and molecular profiles of whole tumours, allowing researchers to discover important information about the tumour cells. In addition, they provide an opportunity to explore the healthy cells surrounding the tumour, thereby establishing a picture of the interactions between the tumour and the microenvironment in which it exists, which is important information that could be exploited for treatments methods. Using the omics approach, the researchers have been able to identify and describe the functions of the metabolites contributing to the malignant progression of cancer cells. They found that hypoxia, nutrient starvation and acidic pH all induce tumour aggressiveness by epigenetic regulation. Osawa and the team now want to identify further cancer metabolites that lead to malignancy and, ultimately, develop therapeutics for metastasis and recurrent advanced cancer from the viewpoint of an integrative multiomics approach.

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MiR-122 Promotes the Development of Colon Cancer by Targeting ALDOA In Vitro

Technology in Cancer Research & Treatment ◽

10.1177/1533033819871300 ◽

2019 ◽

Vol 18 ◽

pp. 153303381987130 ◽

Cited By ~ 2

Author(s):

Hong Li ◽

Xinhua Zhang ◽

Zhao Jin ◽

Tao Yin ◽

Chuanyi Duan ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Biology ◽

Quantitative Polymerase Chain Reaction ◽

Treatment Options ◽

Colon Cancer Cells ◽

Diagnosis And Prognosis ◽

Functional Relevance ◽

Sw620 Cells

Non-coding RNAs, originally considered junk gene products, have taken center stage in view of their significant involvement in a spectrum of biological processes during human development, thereby offering novel therapeutic targets for improvement of treatment options. Accumulating evidence has demonstrated non-coding RNA dysfunction across various human cancers. In particular, microRNAs have emerged as key regulatory molecules in cancer biology. MicroRNAs are noninvasive, readily accessible biomarkers that can be effectively applied for diagnosis and prognosis of different tumor types, including colon cancer. In this study, we reanalyzed the available data with bioinformatics tools to identify differentially expressed microRNAs in colon cancer cells. The top 3 upregulated microRNAs (miR-10, miR-199, and miR-122) in colon cancer cells were further validated in tissues of clinical patients via reverse transcription-quantitative polymerase chain reaction. Our results showed that miR-122 significantly promotes the proliferation and invasion ability of SW480 and SW620 cells through inhibition of Aldolase, Fructose-Bisphosphate A ( ALDOA) expression. We further summarized recent advances in our understanding of the functional relevance of microRNAs in cancer development and discussed the possible implications of specific microRNAs in colon cancer. This study extends our knowledge of microRNA involvement in colon cancer biology and presents novel candidates for the development of attractive therapeutic strategies.

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Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

Functional Foods in Health and Disease ◽

10.31989/ffhd.v3i3.64 ◽

2013 ◽

Vol 3 (3) ◽

pp. 66 ◽

Cited By ~ 2

Author(s):

Vanessa Hörmann ◽

Sivanesan Dhandayuthapani ◽

James Kumi-Diaka ◽

Appu Rathinavelu

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Cancer Cells ◽

Apoptotic Cell ◽

Treatment Options ◽

Attractive Alternative ◽

Intrinsic Apoptotic Pathway ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Combination Treatments

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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Vitamin C as an Anticancer Agent: Regulation of Signaling Pathways

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200710102841 ◽

2020 ◽

Vol 20 (21) ◽

pp. 1868-1875

Author(s):

Ghazala Butt ◽

Ammad A. Farooqi ◽

Aima Adylova ◽

Rukset Attar ◽

Seher Yilmaz ◽

...

Keyword(s):

Vitamin C ◽

Cancer Cells ◽

Signaling Pathways ◽

Scientific Evidence ◽

Treatment Options ◽

Published Data ◽

New Era ◽

Molecular Oncology ◽

Anticancer Effects ◽

Oncogenic Pathways

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

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The Mechanism of Lunasin's Effect on the Growth of Breast Cancer Cells Induced by Obesity-induced Inflammation

Impact ◽

10.21820/23987073.2020.7.16 ◽

2020 ◽

Vol 2020 (7) ◽

pp. 16-18

Author(s):

Chia-Chien Hsieh

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Inflammatory Responses ◽

Specific Area ◽

Tumour Microenvironment ◽

Associate Professor ◽

World Health ◽

Cancer Development ◽

Breast Cancer Development

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.

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Epigenetic dysregulation of immune-related pathways in cancer: bioinformatics tools and visualization

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00612-z ◽

2021 ◽

Author(s):

Anders Berglund ◽

Ryan M. Putney ◽

Imene Hamaidi ◽

Sungjune Kim

Keyword(s):

Patient Outcome ◽

Immune Responses ◽

Cancer Cells ◽

Immune Evasion ◽

Epigenetic Regulation ◽

Current Evidence ◽

Immune Recognition ◽

Bioinformatics Tools ◽

Visualization Techniques ◽

Cancer Bioinformatics

AbstractCancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.

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Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate

Scientific Reports ◽

10.1038/s41598-021-84421-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benedikt Feuerecker ◽

Philipp Biechl ◽

Christof Seidl ◽

Frank Bruchertseifer ◽

Alfred Morgenstern ◽

...

Keyword(s):

Amino Acids ◽

Cancer Cells ◽

Treatment Response ◽

Cell Lines ◽

Egf Receptor ◽

Metabolic Response ◽

Gas Chromatography Mass Spectrometry ◽

Alpha Emitter ◽

Early Treatment Response ◽

Bladder Cancer Cells

AbstractEvaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography–mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail.

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Targeted metabolomics in the cell culture media reveals increased uptake of branched amino acids by breast cancer cells

Analytical Biochemistry ◽

10.1016/j.ab.2021.114192 ◽

2021 ◽

pp. 114192

Author(s):

Fang Kou ◽

Bangjie Zhu ◽

Wenbin Zhou ◽

Chunming Lv ◽

Yu Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Amino Acids ◽

Cell Culture ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Culture Media ◽

Targeted Metabolomics ◽

Cell Culture Media ◽

Branched Amino Acids

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Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer

Metabolites ◽

10.3390/metabo11040216 ◽

2021 ◽

Vol 11 (4) ◽

pp. 216

Author(s):

Mio Harachi ◽

Kenta Masui ◽

Webster K. Cavenee ◽

Paul S. Mischel ◽

Noriyuki Shibata

Keyword(s):

Cancer Cells ◽

Intracellular Signaling ◽

Cancer Biology ◽

High Resolution Mass Spectrometry ◽

Metabolic Reprogramming ◽

Protein Acetylation ◽

Protein Activity ◽

Oncogenic Signaling ◽

Intermediary Metabolites ◽

Novel Therapeutic Strategies

Metabolic reprogramming is an emerging hallmark of cancer and is driven by abnormalities of oncogenes and tumor suppressors. Accelerated metabolism causes cancer cell aggression through the dysregulation of rate-limiting metabolic enzymes as well as by facilitating the production of intermediary metabolites. However, the mechanisms by which a shift in the metabolic landscape reshapes the intracellular signaling to promote the survival of cancer cells remain to be clarified. Recent high-resolution mass spectrometry-based proteomic analyses have spotlighted that, unexpectedly, lysine residues of numerous cytosolic as well as nuclear proteins are acetylated and that this modification modulates protein activity, sublocalization and stability, with profound impact on cellular function. More importantly, cancer cells exploit acetylation as a post-translational protein for microenvironmental adaptation, nominating it as a means for dynamic modulation of the phenotypes of cancer cells at the interface between genetics and environments. The objectives of this review were to describe the functional implications of protein lysine acetylation in cancer biology by examining recent evidence that implicates oncogenic signaling as a strong driver of protein acetylation, which might be exploitable for novel therapeutic strategies against cancer.

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