Biological Activity of Agaricinic Acid Nanoparticles against Human Hepatoma HepG2 Cells
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 4, August, 2020
BIOTECHNOLOGIES Biological Activity of Agaricinic Acid Nanoparticles against Human Hepatoma HepG2 Cells
O. I. Gudkova1, A. G. Demchenko1, A. V. Shvets1, V. N. Kuryakov2, N. E. Sedyakina1, A. V. Lyundup1, N. B. Feldman1, T. I. Gromovykh1, and S. V. Lutsenko1 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 4, pp. 495-498, April, 2020 Original article submitted June 10, 2019 A stable preparation of agaricinic acid nanoparticles was obtained. The mean hydrodynamic size of nanoparticles according to photon correlation spectroscopy was 200 nm and zeta potential was -57 mV. Cytotoxic activity of agaricinic acid nanoparticles against human HepG2 hepatoma cells was evaluated. Nanoparticles with a low concentration of agaricinic acid stimulated and with high concentration — suppressed metabolic activity and viability of hepatoma cells. The EC50 for the stimulating effect was 32.8 µg/ml, and the IC50=602.1 mg/ ml. The preparation of agaricinic acid nanoparticles can be used in medicine as a potential antitumor agent. Key Words: agaricinic acid; nanoparticles; cytotoxicity; EC50; IC50 The fruiting bodies of basidiomycete Fomitopsis officinalis, along with other biologically active substances, contain agaricinic acid; biological activity of this substance is still poorly studied [13]. In early studies, the inhibitory effect of agaricinic acid on lipid metabolism and steroid biosynthesis was described [11]. Agaricinic acid can also affect permeability of large Ca2+-dependent mitochondrial permeability transition pore (mPTP) that plays an important role in calcium exchange between the mitochondria and cytoplasm [2,4,6]. A key component of mPTP supplying ADP to the mitochondria is adenine nucleotide translocase (ANT) that acts as an ATP/ADP antiporter. Disruption of ANT function can lead to cessation of ATP synthesis in mitochondria and energy starvation of the cell [7,10]. Agaricinic acid binds to ANT through the ciI. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University); 2Oil and Gas Research Institute, Russian Academy of Sciences, Moscow, Russia. Address for correspondence: [email protected]. N. B. Feldman
trate part of the molecule, while the aliphatic sequence C16H33 (Fig. 1) stabilizes its binding by anchoring in the phospholipid bilayer of the mitochondrial membrane [6]. By acting in this way, agaricinic acid induces pore opening in the inner membrane, which leads to Ca2+ release from the mitochondria, a drop in the membrane potential, massive influx of water and ions into the mitochondrial matrix, mitochondrial swelling, and rupture of the outer membrane. As a result, proteins that initiate the process of apoptosis, can be released from mitochondria [3,12,15]. The mechanism of the modulating effect of agaricinic acid on the mitochondrial pore can be more complex. It was demonstrated
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Fig. 1. Molecular structure of agaricinic (2-hydroxy-1,2,3
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