Next Article in Journal
Fluorinated Polyurethanes, Synthesis and Properties
Next Article in Special Issue
Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity
Previous Article in Journal
Correction: Van der Merwe, J.D., et al. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status. Molecules 2015, 20, 22674–22690
Previous Article in Special Issue
Cytotoxic Alkaloids from the Stem of Xylopia laevigata
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(7), 906; doi:10.3390/molecules21070906

The Interference of Selected Cytotoxic Alkaloids with the Cytoskeleton: An Insight into Their Modes of Action

Department of Biology, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 20 June 2016 / Revised: 5 July 2016 / Accepted: 6 July 2016 / Published: 12 July 2016
(This article belongs to the Special Issue Diversity of Alkaloids)
View Full-Text   |   Download PDF [5772 KB, uploaded 12 July 2016]   |  

Abstract

Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine), which are known to affect neuroreceptors, protein biosynthesis and nucleic acids, also interact with the cellular cytoskeleton, such as microtubules and actin filaments, as well. Sanguinarine, chelerythrine and chelidonine depolymerized the microtubule network in living cancer cells (Hela cells and human osteosarcoma U2OS cells) and inhibited tubulin polymerization in vitro with IC50 values of 48.41 ± 3.73, 206.39 ± 4.20 and 34.51 ± 9.47 μM, respectively. However, sanguinarine and chelerythrine did not arrest the cell cycle while 2.5 μM chelidonine arrested the cell cycle in the G2/M phase with 88.27% ± 0.99% of the cells in this phase. Noscapine and protopine apparently affected microtubule structures in living cells without affecting tubulin polymerization in vitro, which led to cell cycle arrest in the G2/M phase, promoting this cell population to 73.42% ± 8.31% and 54.35% ± 11.26% at a concentration of 80 μM and 250.9 μM, respectively. Homoharringtonine did not show any effects on microtubules and cell cycle, while the known microtubule-stabilizing agent paclitaxel was found to inhibit tubulin polymerization in the presence of MAPs in vitro with an IC50 value of 38.19 ± 3.33 μM. Concerning actin filaments, sanguinarine, chelerythrine and chelidonine exhibited a certain effect on the cellular actin filament network by reducing the mass of actin filaments. The interactions of these cytotoxic alkaloids with microtubules and actin filaments present new insights into their molecular modes of action. View Full-Text
Keywords: alkaloids; sanguinarine; chelerythrine; chelidonine; noscapine; protopine; homoharringtonine; paclitaxel; microtubules; actin filaments alkaloids; sanguinarine; chelerythrine; chelidonine; noscapine; protopine; homoharringtonine; paclitaxel; microtubules; actin filaments
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, X.; Tanaka, M.; Krstin, S.; Peixoto, H.S.; Wink, M. The Interference of Selected Cytotoxic Alkaloids with the Cytoskeleton: An Insight into Their Modes of Action. Molecules 2016, 21, 906.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top