Cell lines

C6 cells

Preparation method

The solubility of this compound in sterile water is 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

2.5, 5 or 10 μM

Applications

Compared with no treatment, Lactacystin significantly inhibited the proliferation of C6 cells at the 3 indicated doses. In addition, Lactacystin at all concentrations also significantly increased the number of apoptotic cells and decreased mitochondrial membrane potential when compared with the control group.

Animal models

Nude mice bearing gliomas

Dosage form

1.0 μg or 5.0 μg per 20 g body weight; i.p.; q.d., for 7 days

Applications

In nude mice bearing gliomas, Lactacystin significantly inhibited tumor growth. However, at day 17, tumor volume increased to baseline in all experimental groups. On day 9 after termination of Lactacystin treatment, the tumor staining results revealed that Lactacystin significantly increased the mRNA and protein levels in the ratio of Bax to Bcl-2.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

• Front Cell Infect Mi (2022): 1349.

Lactacystin is a microbial metabolite isolated from Streptomyces that is now widely used as a selective inhibitor of the 20S proteasome.[1],[2],[3] Lactacystin was first characterized by its ability to induce differentiation and inhibit cell cycle progression in several tumor cell lines. At concentrations from 2 to 10 μM, lactacystin induces the outgrowth of neurites in the neuroblastoma cell line Neuro2a.4 Lactacystin irreversibly alkylates subunit X of the 20S proteasome.[3] The concomitant inhibition of proteasome peptidase activity results in the accumulation of a variety of ubiquitinated proteins which would normally undergo rapid degradation. Thus, the effects of lactacystin are pleiotropic and depend substantially on the expression pattern of signalling proteins within the treated cell.

Reference:
[1]. Omura, S., Fujimoto, T.T., Otoguro, K., et al. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells. Journal of Antibiotics 44, 113-116 (1991).
[2]. Corey, E.J., and Reichard, G.A. Total synthesis of lactacystin. Journal of the American Chemical Society 114, 10677-10678 (1992).
[3]. Fenteany, G., and Schreiber, S.L. Lactacystin, proteasome function, and cell fate. The Journal of Biological Chemisty 273(15), 8545-8548 (1998).
[4]. Fenteany, G., Standaert, R.F., Reichard, G.A., et al. A β-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line. Proceedings of the National Academy of Sciences of the United States of America 91, 3358-3362 (1994).