The anticancer drugs camptothecin (CPT) and topotecan (TPT) are known DNA topoisomerase I inhibitors which cause DNA damage and lead to cell death. In this study we provide evidence that CPT and TPT also interfere with the elements of cytoskeleton - microtubules and actin filaments which could be partly responsible for their cytotoxic properties. CPT and TPT apparently affected microtubule structures in living cells (Hela and U2OS) and inhibited tubulin polymerization in vitro with IC50 values of 74.57±9.96µM and 121.55±58.68µM, respectively. TPT significantly affected the nucleation and growth phase during the microtubule assembly in vitro, whereas the mode of action of CPT was different in that it specifically affected the 'tread milling' of polymerized microtubules. Cell cycle effects of CPT and TPT varied with their concentrations. CPT and TPT induced G2/M arrest and promoted the population to 76.94±11.20% and 83.91±2.43% at a concentration of 9.4nM and 46.9nM, respectively. As the concentration increased, cells were blocked in S phase with a dose-dependent reduction in G2/M population. In addition, CPT and TPT exhibited a certain effect on actin filaments by reducing the mass of actin filaments. The interactions of CPT and TPT with microtubules and actin filaments present new insights into their modes of action.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2016.07.044 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Total glucosides of paeony ameliorates chemotherapy-induced neuropathic pain by suppressing microglia pyroptosis through the inhibition of KAT2A-mediated p38 pathway activation and succinylation.
Sci Rep
December 2024
Department of Anesthesiology, Qianxi People's Hospital, No. 38 Lisha East Road, Qianxi, Bijie, Guizhou, China.
Chemotherapy-induced neuropathic pain (CINP) is a prevalent side effect of chemotherapy. Total glucosides of paeony (TGP) have been shown to be effective in pain management. This study aimed to investigate the efficacy and mechanism of TGP in alleviating CINP.
View Article and Find Full Text PDFIdentification of 7-aminourea or 7-aminothiourea derivatives of camptothecin as selective topoisomerase I inhibitors with anti-colorectal cancer activities.
Bioorg Chem
November 2024
School of Pharmacy, Lanzhou University, No. 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address:
Colorectal cancer (CRC) remains one of the most prevalent malignant tumors of the digestive system, yet the availability of safe and effective chemotherapeutic agents for clinical use remains limited. Camptothecin (CPT) and its derivatives, though approved for cancer treatment, have encountered significant challenges in clinical application due to their low bioavailability and high systemic toxicity. Strategic modification at the 7-position of CPT enables the development of novel CPT derivatives with high activity.
View Article and Find Full Text PDFInfluence of Chairside Simulated Adjustment (Finishing and Polishing) Protocol and Chlorhexidine Mouthwash Immersion on Color Stability and Translucency of 2 and 3 Preshaded Multilayered Monolithic Zirconia.
Med Sci Monit
February 2024
Department of Prosthetic Dental Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia.
BACKGROUND Preshaded monolithic zirconia (MLZ) is reported to have high translucency. This study aimed to assess the effect of chlorhexidine gluconate (ChG) mouthwash on color and translucency parameter (TP) of 2 different preshaded MLZ dental ceramics after clinical adjustment. MATERIAL AND METHODS Two MLZ disk-shaped specimens [NPM (Nacera Pearl Multi-Shade) (n=72) and CZM (Ceramill Zolid FX Multilayer)] (n=72) were simulated for clinical adjustment, finished, and polished using 2 adjustment kits [recommended kit, third-party kit: Diasynt Plus and SUN (n=12 each)] and later immersed in ChG mouthwash (Avohex) for 2 weeks.
View Article and Find Full Text PDFFacile synthesis and cytotoxicity of substituted uracil-1'()-acetic acid and 4-pyridone-1'()-acetic acid esters of 20(S)-camptothecins.
J Asian Nat Prod Res
February 2024
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
A series of novel substituted uracil-1'()-acetic acid esters (-) and 4-pyridone-1'()-acetic acid esters (-) of 20(S)-camptothecins (CPTs) have been synthesized by the acylation method. All of these new esters were assayed for cytotoxicity against five human cancer cell lines A549, Bel7402, BGC-823, HCT-8 and A2780. The bioassay results showed that all the synthesized compounds - had cytotoxities that were higher than TPT and comparable to CPT on these five tumor cell lines, some of them even showed comparable or superior cytotoxic activity to CPT.
View Article and Find Full Text PDFMulti-index fuzzy comprehensive evaluation model with information entropy of alfalfa salt tolerance based on LiDAR data and hyperspectral image data.
Front Plant Sci
August 2023
Key Laboratory of 3D Information Acquisition and Application, Ministry of Education, Capital Normal University, Beijing, China.
Rapid, non-destructive and automated salt tolerance evaluation is particularly important for screening salt-tolerant germplasm of alfalfa. Traditional evaluation of salt tolerance is mostly based on phenotypic traits obtained by some broken ways, which is time-consuming and difficult to meet the needs of large-scale breeding screening. Therefore, this paper proposed a non-contact and non-destructive multi-index fuzzy comprehensive evaluation model for evaluating the salt tolerance of alfalfa from Light Detection and Ranging data (LiDAR) and HyperSpectral Image data (HSI).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!