The glucose level and gamma-glutamyl transpeptidase activity in hepatocyte-like cells under the action of extracts and cytokinin fractions of medicinal mushrooms

N. Vedenicheva, G. Al-Maali, L. Коt, L. Ostapchenko, L. Garmanchuk
Kholodny Institute of Botany of NAS of Ukraine, Kyiv; Kholodny Institute of Botany of NAS of Ukraine, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv


Mushroom extracts show the multifunctional activity and have a wide range of applications for the treatment of various diseases, including cancer. However, the full composition of the compounds that produce macromycetes that exhibit antitumor properties has not yet been established. Impaired glucose metabolism and activation of gamma-glutamyltranspeptidase (GGT) in tumor cells may be a key marker of biochemical anaplasia in neoplasms. The aim of the study was to investigate the effect of crude extracts and cytokinin fractions isolated from the mycelial biomass of medicinal mushrooms on the biological properties of cells of hepatocyte-like cells of the HepG2 line (human hepatocellular carcinoma). The objects of the research were pure mushroom cultures of Hericium coralloides, Fomitopsis officinalis, Trametes (Coriolus) versicolor, Pleurotus ostreatus and Morchella esculenta. Cytokinin fractions from the extracts were isolated by centrifugation followed by fractionation and purification using ion exchange chromatography. Qualitative and quantitative analysis of cytokinins was performed by high-performance liquid chromatography. GGT activity was determined using the kit "Filisit" (Ukraine), glucose level – glucose oxidase method, with modifications for the cellular culture medium. The analysis of mycelial biomass of medicinal macromycetes revealed the presence of transzeatin, zeatin riboside, zeatin-O-glucoside and isopentenyladenine, that showed high activity in relation to cytokinin synthesis. Inhibition of glucose diffusion from the cultivation medium with the use of crude extracts and cytokinin fractions of medicinal mushroom and a decrease in GGT activity, more pronounced with the action of cytokinin fractions, compared with crude extracts, was noted. The difference between the effects of crude extracts and cytokinin fractions indicated the complex nature of the action of biologically active substances of medicinal mushroom. Presented results regarding the effects of crude extracts and cytokinin fractions of medicinal mushroom showed a normalizing effect on the main metabolic parameters which change in tumor cells, as a mechanism of biochemical anaplasia.


Glucose; cytokinins; gamma-glutamyl transpeptidase activity; HepG2 cells; medicinal mushrooms

Full Text:



Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. 2013;21(3):297-308.

Hanigan MH, Gallagher BC, Townsend DM, Gabarra V. γ-glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo. Oxford J. 1999;20(4):553-559.

Corti A, Franzini M, Paolicchi A, Pompella A. Gamma-glutamyltransferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting. Anticancer Res. 2010;30(4):69-81.

Okon IS, Zou M-H. Mitochondrial ROS and cancer drug resistance: Implications for therapy. Pharmacol Res. 2015;100:170-174.

Chopra H, Mishra AK, Baig AA, Mohanta TK, Mohanta YK, Baek K-H. Narrative review: bioactive potential of various mushrooms as the treasure of versatile therapeutic natural product. J Fungi. 2021;7:728. 10.3390/jof7090728.

Wasser SP. Medicinal mushrooms in human clinical studies. Part I. Anticancer, oncoimmunological and immunomodulatory activities: a review. Int J Med Mushrooms. 2017:19(4):279-317.

Zmitrovich IV, Belova NV, Balandaykin ME, Bondartseva MA, Wasser SP. Cancer without pharmacological illusions and a niche for mycotherapy (review). Int J Med Mushrooms. 2019;21(2):105-119.

Blagodatski A, Yatsunskaya M, Mikhailova V, et al. Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy. Oncotarget. 2018;9(49):29259-29274.

Panda MK, Paul M, Singdevsachan SK, Tayung K, Das SK, Thatoi H. Promising anti-cancer herapeutics from mushrooms: current findings and future perceptions. Curr. Pharm. Biotechnol. 2021;22(9):1164-1191.

Vedenicheva NP, Kosakivska IV. Cytokinins as regulators of plant ontogenesis under different growth conditions. Kyiv: Nash Format; 2017. 200 p.

Voller J, Zatloukal M, Lenobel R, et al. Anticancer activity of natural cytokinins: a structure – activity relationship study. Phytochemistry. 2010;71:1350-1359.

Bisko NA, Lomberg ML, Mytropolska NYu, Mykchaylova O.B. Thе IBK mushroom culture collection. Kyiv: Alterpress; 2016. 120 p.

Vedenicheva NP, Al-Maali GA, Mytropolska NYu, et al. Endogenous cytokinins in medicinal basidiomycetes mycelial biomass. Biotechnol Acta. 2016;9(1):55-63.

Nikolaienko Т, Petruk N, Shelest D, Garmanchuk L. Influence of VEGF, EGF and their antagonists on proliferative activity and glucose consumption by endothelial cells. Bull. T. Shevchenko Nat. Univ. Kyiv. 2015;69(1):36-38.

Castiglioni S, Casati S, Ottria R, et al. N6-isopentenyladenosine and its analogue N6-benzyladenosine induce cell cycle arrest and apoptosis in bladder carcinoma T24 cells. Anti-Cancer Agents Med Chem. 2013;13:672-678.

Spinola M, Colombo F, Falvella FS, Dragani TA. N6-isopentenyladenosine: a potential therapeutic agent for a variety of epithelial cancers. Int J Cancer. 2007;120:2744-2748.

Colombo F, Falvella FS, De Cecco L, et al. Pharmacogenomics and analogues of the antitumour agent N6–isopentenyladenosine. Int J Cancer. 2009;124:2179-2185.

Li M, Qi Y, Wei J, Lu L, Zhao X, Zhou L. N6-isopentenyladenosine promoted HeLa cell apoptosis through inhibitions of AKT and transforming growth factor β-activated kinase 1 activation. Tumor Biol. 2017.

Ranieri R, Ciaglia E, Amodio G, et al. N6-isopentenyladenosine dual targeting of AMPK and Rab7 prenylation inhibits melanoma growth through the impairment of autophagic flux. Cell Death Differ. 2018;25:353-367.

Wang L, Yu DL, Zhang HW, He LYu, Wu L. Orto-topolin riboside induces apoptosis in acute myeloid leukemia HL-60 cells. Mol Cell Toxicol. 2016;12(2):159-166.

Voller J, Béres T, Zatloukal M, Džubák P, et al. Anti-cancer activities of cytokinin ribosides. Phytochem Rev. 2019;18:1101-1113.

Drenichev MS, Oslovsky VE, Mikhailov SN. Cytokinin nucleosides – natural compounds with a unique spectrum of biological activities. Curr Top Med Chem. 2016;16(23):2562-2576.

Chang YY, Zhang M, Jiang YF, et al. Preclinical and clinical studies of Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Discov Med. 2017;23(127):207-219.

Li JF. Biological characteristics, pharmacological action and application prospect of Coriolus versicolor. J Anhui Agri Sci. 2003;1(3):509-510.

Dou H, Chang Y, Zhang L. Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Prog Mol Biol Transl Sci. 2019;163:361-381.

Habtemariam S. Trametes versicolor (Synn. Coriolus versicolor) polysaccharides in cancer therapy: targets and efficacy. Biomedicines. 2020;8(5):135. doi:10.3390/biomedicines8050135.

Tong H, Xia F, Feng K, et al. Structural characterization and in vitro antitumor activity of a novel polysaccharide isolated from the fruiting bodies of Pleurotus ostreatus. Bioresour Technol. 2009;100:1682-1686.

Facchini JM, Alves EP, Aguilera C, et al. Antitumor activity of Pleurotus ostreatus polysaccharide fractions on Ehrlich tumor and Sarcoma 180. Int J Biol Macromol. 2014;68:72-77.

Cao X, Liu J, Yang W, Hou X, Li Q. Antitumor activity of polysaccharide extracted from Pleurotus ostreatus mycelia against gastric cancer in vitro and in vivo. Mol Med Reports. 2015;12:2383-2389.

Lee SR, Roh HS, Lee S, et al. Bioactivity-guided isolation and chemical characterization of antiproliferative constituents from morel mushroom (Morchella esculenta) in human lung adenocarcinoma cells. J Funct Foods. 2018;40:249-260.

Hu M, Chen Y, Wang C, et al. Induction of apoptosis in HepG2 cells by polysaccharide MEP-II from the fermentation broth of Morchella esculenta. Biotechnol Lett. 2013;35:1-10.

Liu C, Sun Y, Mao Q, et al. Characteristics and antitumor activity of Morchella esculenta polysaccharide extracted by pulsed electric field. Int J Mol Sci. 2016;17:986.

Wu H, Chen J, Li J, Liu Y, Park HJ, Yang L. Recent advances on bioactive ingredients of Morchella esculenta. Appl Biochem Biotechnol. 2021. doi: 10.1007/s12010-021-03670-1.

Vedenicheva NP, Al-Maali GA, Bisko NA, Kosakivska IV, Ostrovska GV, Khranovska NM, Horbach OI, Garmanchuk LV, Ostapchenko LI. Effect of cytokinin-containing extracts from some medicinal mushrooms mycelia on HepG2 cells in vitro. Intern J Med Mushrooms. 2021;23(3):15-28.

Marroquin LD, Hynes J, Dykens JA, Jamieson JD, Will Y. Circumventingthe crab tree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicol Sci. 2007;97:539-547.

Gerets HHJ, Tilmant K, Gerin B, et al. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012;28:69-87.

Kamalian L, Chadwick AE, Bayliss M, et al. The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicol in Vitro. 2015;29:732-740.

Received in the editorial 22.09.2021

Received version on 22.10.2021

Signed in the press on 22.10.2021



  • There are currently no refbacks.

Лицензия Creative Commons
This journal is available according to the Creative Commons License «Attribution» («Атрибуція») 4.0 Global (CC-BY).