Lectin with Sialic Acid Specificity Blocks Melanoma Metastasis in Mouse Model

A lectin isolated from the seeds of the Maackia amurensis tree blocks the migration of melanoma cells both in culture dishes and in a mouse skin-cancer model.

Maackia amurensis has been used as a medicinal plant for several centuries to treat ailments including cancer in parts of Asia. Modern studies point to a lectin, MASL, with specificity for alpha-2,3-sialic acid residues as being the medically active component. Lectins are plant proteins or glycoproteins that bind with high specificity to sugar moieties such as those found on cell membrane surface glycoproteins.

Investigators at the University of Medicine and Dentistry of New Jersey (Newark, USA) treated melanoma cell cultures with MASL and treated mice with skin cancer with oral doses of MASL over a period of three weeks. The combination of MASL and melanoma was selected for study because prior research had shown that motility of melanoma cells was regulated by the mucin-receptor protein podoplanin (PDPN). PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. The extracellular domain of PDPN is highly O-glycosylated with alpha-2,3-sialic acid linked to galactose.

Results reported in the July 23, 2012, online edition of the journal PLoS ONE revealed that MASL inhibited melanoma cell growth, migration, and tumorigenesis under the controlled conditions of cell culture. What was more surprising was that the lectin effectively blocked melanoma metastasis in the skin after passing through the digestive tracts of the mice. Of critical importance to future drug development was the finding that MASL caused no notable toxic effects on organ morphology or animal behavior over the three-week period of treatment.

“Cells, even when they are cancerous, tend to stay put,” said senior author Dr. Gary Goldberg, professor of molecular biology at the University of Medicine and Dentistry of New Jersey. “PDPN allows tumor cells to break out of their microenvironment, invade new areas, and metastasize. Our laboratory research shows that MASL not only significantly reduces cell migration it also inhibits cancer cell growth. The absence of any noticeable side effects is not surprising. For centuries, MASL has been taken as a component in medicinal plant extracts used to treat a variety of ailments including cancer. According to standard traditional protocols, these preparations contain very high doses of MASL, yet we cannot find any reports of toxicity from its use.”

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University of Medicine and Dentistry of New Jersey