Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa

Abstract

The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe 3 O 4 /MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3−7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.

Peniapyrones A–I, Cytotoxic Tricyclic-Fused α-Pyrone Derivatives from an Endophytic Penicillium brefeldianum F4a

“…Compounds 1 – 9 were evaluated for their cytotoxic activities against AsPC-1, CRL-2234, and MCF-7 cells; among them, there is a KRAS mutation cell line (ASPC-1 cells). Dasatinib and gemcitabine were used as positive controls. , The detailed methodology was described in a previous publication. ,, …”