Using Maackia Amurensis Seed Lectin to Target the Podoplanin Receptor As a Functionally Relevant Biomarker to Inhibit the Growth of Oral Squamous Cell Carcinoma and Precancerous Lesions

This project will evaluate the expression of a receptor called podoplanin (PDPN) in cells from oral cancers and precancerous lesions. We will also determine how sensitive oral cancer cells are to a potential drug called Maackia amurensis seed lectin (MASL).

开始日期2021-01-29

申办/合作机构

Rowan University

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100 项与 Maackia amurensis seed lectin 相关的临床结果

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100 项与 Maackia amurensis seed lectin 相关的转化医学

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100 项与 Maackia amurensis seed lectin 相关的专利（医药）

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项与 Maackia amurensis seed lectin 相关的文献（医药）

2022-12-01·Biochemistry and Biophysics Reports

Maackia amurensis seed lectin (MASL) ameliorates articular cartilage destruction and increases movement velocity of mice with TNFα induced rheumatoid arthritis

Article

作者: Greenspan, Amanda A ; Bottaro, Andrea ; Hamilton, Kelly L ; Shienbaum, Alan J ; Goldberg, Gary S ; Fischer, Bradford D

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. For example, the transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN on chondrocytes to decrease inflammatory signaling cascades and reduce cartilage destruction in a lipopolysaccharide induced osteoarthritis mouse model. Here, we investigated the effects of MASL on rheumatoid arthritis progression in a TNFα transgenic (TNF-Tg) mouse model. Results from this study indicate that MASL can be administered orally to ameliorate joint malformation and increase velocity of movement exhibited by these TNF-Tg mice. These data support the consideration of MASL as a potential treatment for rheumatoid arthritis.

2021-06-01·Experimental Cell Research3区 · 医学

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

3区 · 医学

Article

作者: Krishnan, Harini ; Balachandran, Premalatha ; Russo, Riccardo ; Kumar, Pradeep ; Retzbach, Edward P ; Suryavanshi, Shraddha ; Hamilton, Kelly L ; Leone, Paola ; Lopez-Gonzalez, Moises ; Sheehan, Stephanie A ; Goldberg, Gary S

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.

2021-02-01·Journal of Cancer Research and Clinical Oncology3区 · 医学

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

3区 · 医学

Article

作者: Tempera, Patrick J ; Hamilton, Kelly L ; Sheehan, Stephanie A ; Goldberg, Gary S ; Timmerman, Clinton A ; Retzbach, Edward P ; Gianneschi, Garret B ; Balachandran, Premalatha

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.

100 项与 Maackia amurensis seed lectin 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
癌前状态	临床1期	美国	Rowan University	2021-01-29
头颈部鳞状细胞癌	临床1期	美国	Rowan University	2021-01-29
口腔鳞状细胞癌	临床1期	美国	Rowan University	2021-01-29