Interaction of Aβ peptide with tubulin causes an inhibition of tubulin polymerization and the apoptotic death of cancer cells.

@article{Saha2015InteractionOA,
  title={Interaction of A$\beta$ peptide with tubulin causes an inhibition of tubulin polymerization and the apoptotic death of cancer cells.},
  author={Abhijit Saha and Saswat Mohapatra and Prashant Kurkute and Batakrishna Jana and Prasenjit Mondal and Debmalya Bhunia and Subhajit Ghosh and Surajit Ghosh},
  journal={Chemical communications},
  year={2015},
  volume={51 12},
  pages={
          2249-52
        }
}
We report in this work that the Aβ peptide directly interacts with tubulin close to the vinblastine and GTP/GDP binding site, inhibits the tubulin polymerization rate, induces tubulin aggregation, causes cell shrinking, enhances Mad2, BubR1, p53, and p21 activation in MCF7 cells and induces the apoptotic death of A549, HeLa and MCF7 cells. 
View on PubMed
rsc.org
9 Citations
Background Citations
3
Methods Citations
1

Figures from this paper

9 Citations

Citation Type

Citation Type

Novel tubulin-targeted cell penetrating antimitotic octapeptide.
TLDR
An antimitotic cell penetrating octapeptide containing single Arg amino acid is discovered, which strongly binds with the exchangeable GTP/GDP binding site of tubulin, which significantly inhibits the multicellular tumor spheroid growth of HeLa cells.
In silico design of peptide inhibitors of tubulin: amyloid-β as a lead compound
TLDR
Results indicated that proposed peptides could potentially inhibit nucleotide exchange as Aβ and designed new Aβ-based peptidic inhibitors of tubulin using visual inspection and alanine scanning method.
α-Cyclodextrin Interacts Close to Vinblastine Site of Tubulin and Delivers Curcumin Preferentially to the Tubulin Surface of Cancer Cell.
TLDR
It is shown for the first time that α-CD interacts with tubulin close to the vinblastine site using molecular docking and Förster resonance energy transfer (FRET) experiment and thatα-CD binds with intracellular tubulin/microtubule, which delivers a high amount of curcumin onto the cancer cell, which causes severe disruption of intrACEllular microtubules.
A short GC rich DNA derived from microbial origin targets tubulin/microtubules and induces apoptotic death of cancer cells.
A short GC rich DNA derived from microbial origin interacts with tubulin/microtubules activates p53 over expression and induces apoptotic death of human breast cancer (MCF-7) cells.
Crafting of Neuroprotective Octapeptide from Taxol-Binding Pocket of β-Tubulin.
TLDR
A potential octapeptide is found, which strongly binds to the taxol pocket of β-tubulin, serves as an excellent microtubule stabilizer, increases the expression of acetylated tubulin, and acts as an Aβ aggregation inhibitor and neuroprotective agent.
Designed Tetrapeptide Interacts with Tubulin and Microtubule.
TLDR
It is found that the novel tetrapeptide Ser-Leu-Arg-Pro (SLRP) causes moderate cytotoxicity to the human breast cancer cell, induces the apoptotic death of MCF-7 cell, and activates the tumor suppressor proteins p53 and cyclin-dependent kinase inhibitor 1 (p21).
Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine
TLDR
Cancer cell specific, MUC1 targeted oligonucleotide aptamer conjugated liposome containing a novel combination of peptide‐docetaxel nanoassembly targeted to tubulin is developed, which exerts synergistic anticancer effect, enhances docetaxe sensitivity, disrupts intracellular microtubule networks, activates key mitotic check point proteins, and significantly reduces the tumor mimicking 3D multicellular spheroid sizes.
Enhanced anticancer effect of Combretastatin A-4 phosphate when combined with vincristine in the treatment of hepatocellular carcinoma.
Visualization of Ceramide-Associated Proteins in Ceramide-Rich Platforms Using a Cross-Linkable Ceramide Analog and Proximity Ligation Assays With Anti-ceramide Antibody
TLDR
It is shown that endogenous ceramide is critical for mediating cross-linking of CAPs to pacFACer and that a combination of cross- linking with PLAs (cross-link/PLA) is a novel tool to visualize CAPs and to understand the regulation of protein interaction with ceramide in CRPs.

References

SHOWING 1-10 OF 37 REFERENCES
Perturbation of microtubule polymerization by quercetin through tubulin binding: a novel mechanism of its antiproliferative activity.
TLDR
The data suggest that quercetin inhibits cancer cells proliferation at least in part by perturbing microtubule functions through tubulin binding.
Structural basis for the regulation of tubulin by vinblastine
TLDR
The X-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD) explains vin Blastine-induced tubulin self-association into spiral aggregates at the expense of microtubule growth.
Prion protein inhibits microtubule assembly by inducing tubulin oligomerization.
Alzheimer Aβ disrupts the mitotic spindle and directly inhibits mitotic microtubule motors
TLDR
Together, these results indicate that by disrupting the interaction between specific kinesins and microtubules and by exerting a direct inhibitory effect on the motor activity, excess Ab deregulates the mechanical forces that govern the spindle and thereby leads to the generation of defective mitotic structures.
Novel microtubule polymerization inhibitor with potent antiproliferative and antitumor activity.
TLDR
It is suggested that T115, the lead compound from the series 1-methyl-5-(3-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-4-yl)-1H-indole, is a potential drug candidate for cancer chemotherapy.
Amyloid-β peptide binds to microtubule-associated protein 1B (MAP1B)
Vinblastine-induced formation of tubulin polymers is electrostatically regulated and nucleated.
TLDR
It is concluded that charge-charge interactions play a significant role in the formation of vinblastine-induced polymers, and that their formation is a two-step process resembling a nucleation/elongation mechanism.
Apoptotic Neuronal Cell Death Induced by the Non-fibrillar Amyloid-β Peptide Proceeds through an Early Reactive Oxygen Species-dependent Cytoskeleton Perturbation*
TLDR
The results convey the idea that upon interaction with the plasma membrane, the non-fibrillar Aβ induces a rapid ROS-dependent disorganization of the cytoskeleton, which results in apoptosis.
Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites.
  • B. Bhattacharyya, J. Wolff
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1976
TLDR
It is concluded that vinblastine binding to the high- and low-affinity sites, respectively, accounts for the depolymerization and aggregation behavior of tubulin.
4',6-Diamidino-2-phenylindole, a fluorescent probe for tubulin and microtubules.
...
1
2
3
4
...