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Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.

ABSTRACT: COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

SUBMITTER: Sheehan SA

PROVIDER: S-EPMC7587785 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression.

Project description:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

| S-EPMC8019238 | biostudies-literature

Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways.

Project description:PurposeOral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined.MethodsHere, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level.ResultsMASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ-SMAD, JAK-STAT, and Wnt-βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil.ConclusionsTaken together, results from this study indicate that MASL decreases activity of JAK-STAT, TGFβ-SMAD, and Wnt-βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.

| S-EPMC7855468 | biostudies-literature

Serum glycopattern and Maackia amurensis lectin-II binding glycoproteins in autism spectrum disorder.

Project description:The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Glycosylation modified as many as 70% of all human proteins can sensitively reflect various pathological changes. However, little is known about the alterations of glycosylation and glycoproteins in ASD. In this study, serum glycopattern and the maackia amurensis lectin-II binding glycoproteins (MBGs) in 65 children with ASD and 65 age-matched typically developing (TD) children were compared by using lectin microarrays and lectin-magnetic particle conjugate-assisted LC-MS/MS analyses. Expression of Siaα2-3 Gal/GalNAc was significantly increased in pooled (fold change = 3.33, p < 0.001) and individual (p = 0.009) serum samples from ASD versus TD children. A total of 194 and 217 MGBs were identified from TD and ASD sera respectively, of which 74 proteins were specially identified or up-regulated in ASD. Bioinformatic analysis revealed abnormal complement cascade and aberrant regulation of response-to-stimulus that might be novel makers or markers for ASD. Moreover, increase of APOD α2-3 sialoglycosylation could sensitively and specifically distinguish ASD samples from TD samples (AUC is 0.88). In conclusion, alteration of MBGs expression and their sialoglycosylation may serve as potential biomarkers for diagnosis of ASD, and provide useful information for investigations into the pathogenesis of ASD.

| S-EPMC5423032 | biostudies-literature

Maackia amurensis

Project description:Maackia amurensis Proteome

| PRJNA209706 | ENA

Neuroprotective and Antiherpetic Properties of Polyphenolic Compounds from <i>Maackia amurensis</i> Heartwood.

Project description:In this study, we isolated a new isoflavanostilbene maackiapicevestitol (1) as a mixture of two stable conformers 1a and 1b as well as five previously known dimeric and monomeric stilbens: piceatannol (2), maackin (3), scirpusin A (4), maackiasine (5), and maackolin (6) from M. amurensis heartwood, using column chromatography on polyamide, silicagel, and C-18. The structures of these compounds were elucidated by NMR, HR-MS, and CD techniques. Maksar® obtained from M. amurensis heartwood and polyphenolics 1-6 possessed moderate anti-HSV-1 activity in cytopathic effect (CPE) inhibition and RT-PCR assays. A model of PQ-induced neurotoxicity was used to study the neuroprotective potential of polyphenolic compounds from M. amurensis. Maksar® showed the highest neuroprotective activity and increased cell viability by 18% at a concentration of 10 μg/mL. Maackolin (6) also effectively increased the viability of PQ-treated Neuro-2a cells and the value of mitochondrial membrane potential at concentrations up to 10 μΜ. Maksar® and compounds 1-6 possessed higher FRAP and DPPH-scavenging effects than quercetin. However, only compounds 1 and 4 at concentrations of 10 μM as well as Maksar® (10 μg/mL) statistically significantly reduced the level of intracellular ROS in PQ-treated Neuro-2a cells.

| S-EPMC10056899 | biostudies-literature

Cranberry and grape seed extracts inhibit the proliferative phenotype of oral squamous cell carcinomas.

Project description:Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

| S-EPMC3138501 | biostudies-literature

Effective glycoanalysis with Maackia amurensis lectins requires a clear understanding of their binding specificities.

Project description: Not available

| S-EPMC3130539 | biostudies-literature

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.

Project description:Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.

| S-EPMC4496201 | biostudies-literature

RNA-Seq transcriptome analysis reveals Maackia amurensis leukoagglutinin has antitumor activity in human anaplastic thyroid cancer cells.

Project description:BackgroundLectins are carbohydrate-binding molecules that can bind specifically to the sugar residues of glycoconjugates and are found in almost all organisms. Plant lectins subjected to many studies reported exhibiting anti-cancer activity. This study aimed to investigate the possible molecular mechanisms of Maackia amurensis leukoagglutinin II (MAL-II) treated ATCCs.Methods and resultsWe tested the effects of MAL-II, which is isolated from Amur seeds, on cancerous features of 8505C human anaplastic thyroid cancer cells (ATCCs) on a large scale using RNA-Seq. Transcriptome analysis was performed using Illumina next-generation sequencing technology by using cDNA libraries obtained from total RNA isolates of ATCCs treated with 0.25 µM MAL-II for 24 h. Gene ontology and pathway enrichment analysis were performed for the systematic analysis of gene functions. Moreover, we validated RNA-Seq findings using qPCR. Our results showed that many cancer-related genes such as TENM4, STIM2, SYT12, PIEZO2, ABCG1, SPNS2, ARRB1, and IRX5 were downregulated and many anticancer genes such as HSPA6, G0S2, TNFAIP3, GEM, GADD45G, RND1, SERPINB2, and IL24 were upregulated. Also, pathway enrichment analysis showed that differentially expressed genes were found to be associated with Ras, p53, and apoptosis signaling pathways, which are some important signal transduction pathways in development, proliferation, stem cell control, and carcinogenesis.ConclusionCollectively, our results show that MAL-II treatment reveals significant antitumor activity by changing the expression of many cancer-related genes and implies that MAL-II treatment might be a potential candidate molecule to inhibit the malignancy of human anaplastic thyroid cancer.

| S-EPMC9441018 | biostudies-literature

Anti‑EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas.

Project description:The epithelial cell adhesion molecule (EpCAM) is a calcium‑independent, homophilic, intercellular adhesion factor classified as a transmembrane glycoprotein. In addition to cell adhesion, EpCAM also contributes to cell signaling, differentiation, proliferation, and migration. EpCAM is an essential factor in the carcinogenesis of numerous human cancers. In the present study, we developed and validated an anti‑EpCAM monoclonal antibody (mAb), EpMab‑16 (IgG2a, kappa), by immunizing mice with EpCAM‑overexpressing CHO‑K1 cells. EpMab‑16 specifically reacted with endogenous EpCAM in oral squamous cell carcinoma (OSCC) cell lines in flow cytometry and Western blot analyses. It exhibited a plasma membrane‑like stain pattern in OSCC tissues upon immunohistochemical analysis. The KD for EpMab‑16 in SAS and HSC‑2 OSCC cells were assessed via flow cytometry at 1.1x10‑8 and 1.9x10‑8 M, respectively, suggesting moderate binding affinity of EpMab‑16 for EpCAM. We then assessed whether the EpMab‑16 induced antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) against OSCC cell lines, and antitumor capacity in a murine xenograft model. In vitro experiments revealed strong ADCC and CDC inducement against OSCC cells treated with EpMab‑16. In vivo experiments on OSCC xenografts revealed that EpMab‑16 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that EpMab‑16 could be a promising treatment option for EpCAM‑expressing OSCCs.

| S-EPMC7640354 | biostudies-literature

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