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Updated: Jul 11, 2025

Author Spotlight: Developing Multiplexed Kinetic Assays for Organoid-Based Drug Response Analysis
Published on: January 5, 2024
Nanopore-related cellular death through cytoskeleton depolymerization by drug-induced ROS
Yan Zhang1, Renfeng Xu1, Jingjing Wu2
1Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou, 350007, China.
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.
Insights
Atomic force microscopy visualized paclitaxel-induced pores in prostate cancer cells. Reactive oxygen species drive pore formation, offering a new method for evaluating cancer drug therapies.
Area of Science:
- Oncology
- Nanotechnology
- Cell Biology
Background:
- Prostate cancer (PCa) is a prevalent malignancy with ongoing research into drug efficacy and mechanisms.
- Current treatment strategies require further exploration of drug-cell interactions at the molecular level.
Purpose of the Study:
- To investigate the anti-cancer mechanisms of paclitaxel (PTX) on prostate cancer cells using atomic force microscopy (AFM).
- To explore the role of reactive oxygen species (ROS) in PTX-induced cellular damage and membrane alterations.
Main Methods:
- Utilized AFM to visualize morphological changes on PC3M cell membranes after PTX treatment.
- Quantified pore formation in terms of diameter, depth, and number in a concentration- and time-dependent manner.
- Investigated the involvement of ROS by using a ROS scavenger and assessing its effect on pore formation.
Main Results:
- AFM revealed the formation of pore-like structures on PC3M cell membranes following paclitaxel treatment.
- Pore formation exhibited a concentration- and time-dependent relationship with PTX exposure.
- Reactive oxygen species were identified as key mediators in depolymerizing the actin cytoskeleton, leading to membrane damage and pore induction.
- Pretreatment with a ROS scavenger effectively inhibited paclitaxel-induced pore formation.
Conclusions:
- AFM provides a novel nanoscale imaging method for evaluating drug effects on cancer cells.
- Paclitaxel induces cell membrane damage through ROS-mediated mechanisms, involving actin cytoskeleton depolymerization.
- This research offers a new perspective on drug-targeted therapy evaluation for prostate cancer.
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