Glucopiericidin A

Glucopiericidin A is a natural piericidin compound obtained from a marine-derived Streptomyces strain. Glucopiericidin A serves as a glucose transporter (GLUT) chemical probe and suppresses glycolysis. Glucopiericidin A inhibits ATP-dependent filopodia protrusion with Piericidin A (PA; HY-114936) and has no effect alone. Glucopiericidin A induces cell apoptosis through reducing the reactive oxygen species (ROS) level by increasing PRDX1 and exhibits potent antitumor efficacy in ACHN mice xenografts[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Glucopiericidin A has cytotoxicities against three renal carcinoma cell lines, ACHN (IC50=0.21 μM), OS-RC-2 (IC50>100 μM), and 786-O (IC50>100 μM), as well as a normal renal cell line, HK-2 (IC50>100 μM)[2]. Glucopiericidin A (25, 50 nM; 24 h) causes the upregulation of PRDX1 in ACHN cells[2]. Glucopiericidin A (25, 50 nM; 24 h) not only raises the expression of mRNA and protein of PRDX1 but also forces it into the nucleus[2]. Glucopiericidin A (25, 50 nM; 24 h) reduces ROS in normal ACHN cells[2]. Neither Glucopiericidin A (GPA) nor Piericidin A (PA) alone, at concentrations up to 500 nM and 2.3 mM, respectively, shows inhibitory activity. When combined, much lower concentrations of GPA (17 nM) and PA (0.68 nM) produces inhibition of filopodia protrusion[1]. Western Blot Analysis[2] Cell Line: ACHN cells Concentration: 25 and 50 nM Incubation Time: 24 hours Result: Caused the upregulation of PRDX1 in ACHN cells. RT-PCR[2] Cell Line: ACHN cells Concentration: 25 and 50 nM Incubation Time: 24 hours Result: Not only raised the expression of mRNA and protein of PRDX1 but also forced it into the nucleus

Glucopiericidin A (0.8 mg/kg/day; IP; for three weeks) significantly reduces the final tumor weight of the mice[2]. Animal Model: Nude mice bearing ACHN tumor xenografts[2] Dosage: 0.8 mg/kg Administration: IP; daily; for three weeks Result: Significantly reduced the final tumor weight of the mice. Increased the mRNA and protein expression of PRDX1 in tumor tissues.

[1]. Mitsuhiro Kitagawa, et al. Metabolomic identification of the target of the filopodia protrusion inhibitor glucopiericidin A. Chem Biol. 2010 Sep 24;17(9):989-98.

[2]. Xuefeng Zhou, et al. Exploring the Natural Piericidins as Anti-Renal Cell Carcinoma Agents Targeting Peroxiredoxin 1. J Med Chem. 2019 Aug 8;62(15):7058-7069.