Glucosamine sulfate targeted effect in the combination cancer therapy

I.Yu. Torshin^1,2, O.A. Gromova^1,2, A.M. Lila³, A.G. Назаренко⁴, I.S. Romanov⁵, L.E. Fedotova^1,2, A.G. Kalacheva^1,2, I.V. Gogoleva^1,2

¹Federal Research Center “Informatics and Management” of the Russian Academy of Sciences, Moscow

²Big Data Storage and Analysis Center of the Lomonosov Moscow State University

³V.A. Nasonova Research Institute of Rheumatology, Moscow

⁴Burdenko National Medical Research Center for Neurosurgery, Moscow

⁵N.N. Blokhin National Medical Research Center of Oncology, Moscow

Glucosamine sulfate (GS), used in the treatment of joints diseases, contributes to the pro-inflammatory transcription factor NF-κB inhibition.

Aim: to study the GS potential effects on human kinome (the sum of all kinase enzymes).

Patients and Methods: a dose-dependent chemokine analysis of GS effect on 297 kinase enzymes activity was carried out using the analysis theory methods of labeled graphs and the topological analysis theory of poorly formalized recognition problems. To implement chemokine modeling, chemographs theories, chemoinformatic and chemoreactomy analysis methods were used.

Results: kinom experiments results in the Proteomics DB database are presented in tables, in the columns of which human kinases are shown, and in rows — the corresponding molecules, the activity of which was studied relative to the examined kinases set. The table shows the changes in the kinases activity when exposed to the MGS molecule. Each such “chemokine experiment table” corresponds to (1) a method for determining the kinase activity and (2) an acting mo lecules fixed concentration (1, 3, 10, 100, 1000 nmol / l, etc.).

GS can inhibit the 31 human kinases activity with inhibition constant values (EC50) in the submicromolar range. Kinases (MAP3K3, PDPK1, IKBKE) activity suppression corresponds to alternative inhibiting NF-κB ways by means of GS. Inhibiting the activity of cyclin-dependent kinases (CDK4, CDK6 and others), GS inhibits hyperproliferative processes, and the CHEK1, Src and PRKCD kinases inhibition stimulates tumor cells apoptosis. Dose-dependent changes in the levels of proinflammatory cytokine TNF-α and anti-inflammatory interleukin-10 under the GS influence were obtained, confirming the chemokine analysis results.

Conclusion: established profile inhibition of glucosamine sulfate kinases is advisable as part of the combined antitumor therapy for leukemia, breast cancer, colon cancer, melanoma, non-small cell lung cancer. This kinase sampling inhibition also contributes to the reduction of excessive angiogenesis, overcoming metastasis and tolerance to chemotherapy.

Keywords: human kinom, antiproliferative effect, glucosamine sulfate, Sustaguard artro.

For citation: Torshin I.Yu., Gromova O.A., Lila A.M. et al. Glucosamine sulfate targeted effect in the combination cancer therapy. RMJ. 2019;6:23–30.