Lith-o-asp

Lith-O-Asp is a sialytransferase (ST) inhibitor, with IC50s of 12-37 μM.

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

IC50: 12-37 μM (ST)[1].

The results indicate that Lith-O-Asp shows no apparent growth inhibition effect toward different cancer cell lines at the tested doses of 10, 30, and 60 μM. By in vitro activity assay, it is revealed that the ability of Lith-O-Asp to inhibit the activities of ST3Gal I, ST3Gal III, and ST6GalI. The IC50 values ranged from 12 to 37 μM. Flow cytometry shows a significant decrease in the expression of cell surface a-2,3- and a-2,6-sialylated antigens on The results indicates that Lith-O-Asp decreased the activity of both a-2,3- and a-2,6-sialyltransferases, and thus inhibit the transfer of sialic acids to the targeted glycoproteins[1].

A significant amount of secondary metastatic cancer cells are observed in lung tissues of DMSO control mice detected using IVIS in vivo imaging system after 26 days of fat pad inoculation. However, Lith-O-Asp–treated mice show fewer lung metastases. All DMSO-treated mice confirm secondary lung metastasis, but only 3 of 8 Lith-O-Asp-treated mice show lung metastasis. Average tumor nodules per mouse are 11±9 nodules in DMSO-treated group, and 2±4 nodules in Lith-O-Asp-treated group. Additionally, significantly stronger 4T1-Luc illumination signals are shown in control mice than in those injected with Lith-O-Asp-treated cancer cells on days 7 and 9[1].

About 3x104 of the CL1-0, CL1-5, A549, and H1299 lung cancer cells are seeded on 12-well culture dishes in DMEM containing 10% FBS. Different concentrations of Lith-O-Asp (10, 30, and 60 μM) are added into each plate and incubated for 48 hr. Cell viabilities under different concentrations of compound treatment are determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In the untreated control, 0.1% DMSO-containing medium is used[1].

Mice[1] The BALB/c mice are used. Highly metastatic murine 4T1-Luc breast cancer cells (5 x105) are subcutaneously injected into the mammary fat pad of mice. Mice receive 3 mg/kg of Lith-O-Asp intraperitoneally on every other day. DMSO treatment is used as control. The growth and the spontaneous metastasis of the tumors are observed under IVIS50 in vivo imaging system with endotoxin-free luciferase substrate injection. The metastasized tumor tissues are dissected on day 26[1].

[1]. Chen JY, et al. A novel sialyltransferase inhibitor suppresses FAK/paxillin signaling and cancer angiogenesis and metastasis pathways. Cancer Res. 2011 Jan 15;71(2):473-83.

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