A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia
Emmanuel Datan, Il Minn, Peng Xu, Qingli He, Hye-Hyun Ahn, Biao Yu, Martin G. Pomper, Jun O. Liu
Abstract
. Herein, we identified a lead, glutriptolide-2 with an altered linker structure. Glutriptolide-2 possessed improved stability in human serum, greater selectivity toward cancer over normal cells, and increased potency against cancer cells. Glutriptolide-2 exhibits sustained antitumor activity, prolonging survival in a prostate cancer metastasis animal model. Importantly, we found that glutriptolide-2 was more potent against cancer cells under hypoxia than normoxia. Together, this work provides an attractive glutriptolide drug lead and suggests a viable strategy to overcome chemoresistance through conjugation of cytotoxic agents to glucose.
Topics & Concepts
TriptolideConjugateHypoxia (environmental)ChemistryCancer cellCancer therapyBioorganic chemistryCancerBiochemistryBiologyCell biologyApoptosisOxygenGeneticsOrganic chemistryMathematicsMathematical analysisEnzymeNatural Compounds in Disease TreatmentHistone Deacetylase Inhibitors ResearchATP Synthase and ATPases Research