St-N, a novel alkaline derivative of stevioside, reverses docetaxel resistance by targeting lysosomes in vitro and in vivo.

ABSTRACT: Drug resistance of cancers remains a major obstacle due to limited therapeutics. Lysosome targeting is an effective method for overcoming drug resistance in cancer cells. St-N (ent-13-hydroxy-15-kaurene-19-acid N-methylpiperazine ethyl ester) is a novel alkaline stevioside derivative with an amine group. In this study, we found that docetaxel (Doc)-resistant prostate cancer (PCa) cells were sensitive to St-N. Mechanistically, the alkaline characteristic of St-N led to targeting lysosomes, as evidenced by lysosomal swelling and rupture through transmission electron microscopy and Lyso-tracker Red staining. St-N destabilized lysosomal membrane by impairing lysosomal membrane proteins and acid sphingomyelinase. As a result, St-N caused cathepsins to release from the lysosomes into the cytosol

SUBMITTER: Guo Y 

PROVIDER: S-EPMC11676526 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature