Molecular mechanism of anticancer effect ofSclerotium rolfsiilectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis

Barkeer, Srikanth; Guha, Nilanjan; Hothpet, Vishwanathreddy; Adavigowda, Deepak Saligrama; Hegde, Prajna; Padmanaban, Arunkumar; Yu, Lu‐Gang; Swamy, Bale M.

doi:10.1093/glycob/cwv067

Cited by 11 publications

(7 citation statements)

References 73 publications

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“…SRL treatment also downregulated POLA2 101 . POLA2 encodes DNA polymerase α subunit 2 and pairs with PARP to do a DNA damage survey.…”

Section: Dicationmentioning

confidence: 89%

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Revealing ETC-1922159 Affected Unknown 3rd order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

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WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

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“…SRL treatment also downregulated POLA2 101 . POLA2 encodes DNA polymerase α subunit 2 and pairs with PARP to do a DNA damage survey.…”

Section: Dicationmentioning

confidence: 89%

“…Binding of SRL (Sclerotium rolfsii lectin) to human colon has been found to induce cell apoptosis and suppression of tumor growth 101 . SRL treatment also downregulated POLA2 101 .…”

Section: Dicationmentioning

confidence: 99%

Revealing ETC-1922159 Affected Unknown 3rd order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

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“…The lectin elicited apoptosis in human breast, colon, and ovarian cancer cells and exerted an anticancer action in vivo. In human colon cancer HT29 cells, the lectin affected expression of mitogen-activated protein kinase and c-JUN-associated cell proliferation signaling pathways after 2 h. On the other hand, it altered cell miRNA expression 10 h later, and miRNAassociated cell cycle, DNA replication and apoptotic pathways after 1 day (Barkeer et al 2015). Rhizoctonia bataticola lectin exhibited immunopotentiating activity toward normal human peripheral blood mononuclear cells and exerted antiproliferative cytotoxicity on Molt-4 and Jurkat human leukemic T cell lines bringing about apoptosis in 33 and 42 % of the cells, respectively.…”

Section: Fungal Proteins and Peptides With Antitumor Activitymentioning

confidence: 98%

Fungal proteinaceous compounds with multiple biological activities

Cheung

Wong

et al. 2016

Appl Microbiol Biotechnol

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Fungi comprise organisms like molds, yeasts and mushrooms. They have been used as food or medicine for a long time. A large number of fungal proteins or peptides with diverse biological activities are considered as antibacterial, antifungal, antiviral and anticancer agents. They encompass proteases, ribosome inactivating proteins, defensins, hemolysins, lectins, laccases, ribonucleases, immunomodulatory proteins, and polysaccharopeptides. The target of the present review is to update the status of the various bioactivities of these fungal proteins and peptides and discuss their therapeutic potential.

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“…Nine autophagic hub proteins and 13 tumor suppressive miRNA were identified in plant lectin-treated breast carcinoma MCF-7 cells [150]. Using mRNA- and miRNA-microarrays, the SRL (T/Tn-specific Sclerotum rolfsii lectin) treatment of HT29 colon cancer cells resulted in the altered expression of several hundred proteins including MAPK, c-JUN, apoptosis-associated and DNA replication-associated signaling molecules [151]. More recently, up to 22 apoptotic hub proteins were identified in the global human protein-protein interaction network built up for lectin-treated mesothelioma cells according to their different microarray expression, together with the miRNA predicted to negatively regulate these hub proteins [152].…”

Section: Toxic Effects Of Tn/t-specific Lectins On Cancer Cellsmentioning

confidence: 99%

Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

Poiroux

Barre

Damme

et al. 2017

IJMS

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Aberrant O-glycans expressed at the surface of cancer cells consist of membrane-tethered glycoproteins (T and Tn antigens) and glycolipids (Lewis a, Lewis x and Forssman antigens). All of these O-glycans have been identified as glyco-markers of interest for the diagnosis and the prognosis of cancer diseases. These epitopes are specifically detected using T/Tn-specific lectins isolated from various plants such as jacalin from Artocarpus integrifola, and fungi such as the Agaricus bisporus lectin. These lectins accommodate T/Tn antigens at the monosaccharide-binding site; residues located in the surrounding extended binding-site of the lectins often participate in the binding of more extended epitopes. Depending on the shape and size of the extended carbohydrate-binding site, their fine sugar-binding specificity towards complex O-glycans readily differs from one lectin to another, resulting in a great diversity in their sugar-recognition capacity. T/Tn-specific lectins have been extensively used for the histochemical detection of cancer cells in biopsies and for the follow up of the cancer progression and evolution. T/Tn-specific lectins also induce a caspase-dependent apoptosis in cancer cells, often associated with a more or less severe inhibition of proliferation. Moreover, they provide another potential source of molecules adapted to the building of photosensitizer-conjugates allowing a specific targeting to cancer cells, for the photodynamic treatment of tumors.

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Molecular mechanism of anticancer effect ofSclerotium rolfsiilectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis

Cited by 11 publications

References 73 publications

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Fungal proteinaceous compounds with multiple biological activities

Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

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