ArticlePloS one2013
Ansamitocin P3 depolymerizes microtubules and induces apoptosis by binding to tubulin at the vinblastine site.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 58 citations in OpenAlex.
- Maytansinoids in cancer therapy: advancements in antibody-drug conjugates and nanotechnology-enhanced drug delivery systems.Discover oncology · 2025Review
- The response regulator CrsR positively regulates ansamitocin P-3 biosynthesis inFrontiers in microbiology · 2025Article
- Biosynthesis of ansamitocin P-3 incurs stress on the producing strain Actinosynnema pretiosum at multiple targets.Communications biology · 2023Article
- LWJ-M30, a conjugate of DM1 and B6, for the targeted therapy of colorectal cancer with improved therapeutic effects.RSC advances · 2023Article
- Heliotropium ramosissimum metabolic profiling, in silico and in vitro evaluation with potent selective cytotoxicity against colorectal carcinoma.Scientific reports · 2022Article
- Increased yield of AP-3 by inactivation of asm25 in Actinosynnema pretiosum ssp. auranticum ATCC 31565.PloS one · 2022Article
- The Antitumor Agent Ansamitocin P-3 Binds to Cell Division Protein FtsZ inBiomolecules · 2020Article
- Metabolomic change and pathway profiling reveal enhanced ansamitocin P-3 production in Actinosynnema pretiosum with low organic nitrogen availability in culture medium.Applied microbiology and biotechnology · 2020Article
- Article
- Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy.Scientific reports · 2018Article
- A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.Nature communications · 2018Article
- Interaction of microtubule depolymerizing agent indanocine with different human αβ tubulin isotypes.PloS one · 2018Article
- Novel quinolone chalcones targeting colchicine-binding pocket kill multidrug-resistant cancer cells by inhibiting tubulin activity and MRP1 function.Scientific reports · 2017Article
- Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells.Scientific reports · 2017Article
- EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer.International journal of nanomedicine · 2017Article
- C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis.Bioscience reports · 2016Article
- Article
- The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity.Cancer immunology, immunotherapy : CII · 2014Article
- Enhanced anticancer activity of DM1-loaded star-shaped folate-core PLA-TPGS nanoparticles.Nanoscale research letters · 2014Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maytansinoid conjugates are currently under different phases of clinical trials and have been showing promising activity for various types of cancers. In this study, we have elucidated the mechanism of action of ansamitocin P3, a structural analogue of maytansine for its anticancer activity. Ansamitocin P3 potently inhibited the proliferation of MCF-7, HeLa, EMT-6/AR1 and MDA-MB-231 cells in culture with a half-maximal inhibitory concentration of 20±3, 50±0.5, 140±17, and 150±1.1 pM, respectively. Ansamitocin P3 strongly depolymerized both interphase and mitotic microtubules and perturbed chromosome segregation at its proliferation inhibitory concentration range. Treatment of ansamitocin P3 activated spindle checkpoint surveillance proteins, Mad2 and BubR1 and blocked the cells in mitotic phase of the cell cycle. Subsequently, cells underwent apoptosis via p53 mediated apoptotic pathway. Further, ansamitocin P3 was found to bind to purified tubulin in vitro with a dissociation constant (Kd) of 1.3±0.7 µM. The binding of ansamitocin P3 induced conformational changes in tubulin. A docking analysis suggested that ansamitocin P3 may bind partially to vinblastine binding site on tubulin in two different positions. The analysis indicated that the binding of ansamitocin P3 to tubulin is stabilized by hydrogen bonds. In addition, weak interactions such as halogen-oxygen interactions may also contribute to the binding of ansamitocin P3 to tubulin. The study provided a significant insight in understanding the antiproliferative mechanism of action of ansamitocin P3.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.