Nanopore-related cellular death through cytoskeleton depolymerization by drug-induced ROS

Abstract

Prostate cancer (PCa) is a malignant tumor with a very high incidence which ranks second after lung cancer. Although there are many drugs available for the treatment of PCa, their effectiveness and anti-cancer mechanisms still need to be explored. Atomic force microscopy (AFM) could characterize minor morphological changes on cell surfaces, which provides an effective method to explore the interaction between drugs and cells at the nanometer level and further investigate the mechanisms for treating PCa. In our research, AFM visualized pore-like structures in the PC3M cell membrane after treatment with the eminent anticancer agent paclitaxel (PTX). The diameter, depth and number of these pores were in a concentration and time-dependent manner. Reactive oxygen species (ROS) was shown to depolymerize the actin cytoskeleton and make the membrane more sensitive to oxidative damage, thus inducing pore information. After pretreatment with a ROS scavenger, pore formation was prevented. AFM imaging technology provides a new evaluation method for drug-targeted therapy for cancer.