The interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Wang, Xiaojuan (Author) , Tanaka, Mine (Author) , Krstin, Sonja (Author) , Peixoto, Herbenya (Author) , Wink, Michael (Author)
Format: Article (Journal)
Language:English
Published: 12 July 2016
In: Molecules
Year: 2016, Volume: 21, Issue: 7, Pages: 906
ISSN:1420-3049
DOI:10.3390/molecules21070906
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3390/molecules21070906
Get full text
Author Notes:Xiaojuan Wang, Mine Tanaka, Sonja Krstin, Herbenya Silva Peixoto and Michael Wink

MARC

LEADER 00000caa a2200000 c 4500
001 1556004613
003 DE-627
005 20230426153645.0
007 cr uuu---uuuuu
008 170328s2016 xx |||||o 00| ||eng c
024 7 |a 10.3390/molecules21070906  |2 doi 
035 |a (DE-627)1556004613 
035 |a (DE-576)486004619 
035 |a (DE-599)BSZ486004619 
035 |a (OCoLC)1340969115 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 32  |2 sdnb 
100 1 |a Wang, Xiaojuan  |e VerfasserIn  |0 (DE-588)1082261246  |0 (DE-627)847270750  |0 (DE-576)45530288X  |4 aut 
245 1 4 |a The interference of selected cytotoxic alkaloids with the cytoskeleton  |b an insight into their modes of action  |c Xiaojuan Wang, Mine Tanaka, Sonja Krstin, Herbenya Silva Peixoto and Michael Wink 
264 1 |c 12 July 2016 
300 |a 22 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Gesehen am 28.03.2017 
520 |a 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. 
650 4 |a actin filaments 
650 4 |a alkaloids 
650 4 |a chelerythrine 
650 4 |a chelidonine 
650 4 |a homoharringtonine 
650 4 |a microtubules 
650 4 |a noscapine 
650 4 |a paclitaxel 
650 4 |a protopine 
650 4 |a sanguinarine 
700 1 |a Tanaka, Mine  |e VerfasserIn  |0 (DE-588)1104944464  |0 (DE-627)862369819  |0 (DE-576)472957856  |4 aut 
700 1 |a Krstin, Sonja  |e VerfasserIn  |0 (DE-588)1099729076  |0 (DE-627)858744465  |0 (DE-576)469341386  |4 aut 
700 1 |a Peixoto, Herbenya  |e VerfasserIn  |0 (DE-588)1099728886  |0 (DE-627)858744279  |0 (DE-576)469341424  |4 aut 
700 1 |a Wink, Michael  |d 1951-  |e VerfasserIn  |0 (DE-588)124618146  |0 (DE-627)363448519  |0 (DE-576)164659390  |4 aut 
773 0 8 |i Enthalten in  |t Molecules  |d Basel : MDPI, 1996  |g 21(2016,7) Artikel-Nummer 906, 22 Seiten  |h Online-Ressource  |w (DE-627)311313132  |w (DE-600)2008644-1  |w (DE-576)281192456  |x 1420-3049  |7 nnas  |a The interference of selected cytotoxic alkaloids with the cytoskeleton an insight into their modes of action 
773 1 8 |g volume:21  |g year:2016  |g number:7  |g pages:906  |g extent:22  |a The interference of selected cytotoxic alkaloids with the cytoskeleton an insight into their modes of action 
856 4 0 |u http://dx.doi.org/10.3390/molecules21070906  |x Verlag  |x Resolving-System  |z kostenfrei  |3 Volltext 
951 |a AR 
992 |a 20170328 
993 |a Article 
994 |a 2016 
998 |g 124618146  |a Wink, Michael  |m 124618146:Wink, Michael  |d 160000  |d 160100  |d 700000  |d 729400  |e 160000PW124618146  |e 160100PW124618146  |e 700000PW124618146  |e 729400PW124618146  |k 0/160000/  |k 1/160000/160100/  |k 0/700000/  |k 1/700000/729400/  |p 5  |y j 
998 |g 1099728886  |a Peixoto, Herbenya  |m 1099728886:Peixoto, Herbenya  |d 160000  |d 160100  |e 160000PP1099728886  |e 160100PP1099728886  |k 0/160000/  |k 1/160000/160100/  |p 4 
998 |g 1099729076  |a Krstin, Sonja  |m 1099729076:Krstin, Sonja  |d 160000  |d 160100  |e 160000PK1099729076  |e 160100PK1099729076  |k 0/160000/  |k 1/160000/160100/  |p 3 
998 |g 1104944464  |a Tanaka, Mine  |m 1104944464:Tanaka, Mine  |d 160000  |d 160100  |e 160000PT1104944464  |e 160100PT1104944464  |k 0/160000/  |k 1/160000/160100/  |p 2 
998 |g 1082261246  |a Wang, Xiaojuan  |m 1082261246:Wang, Xiaojuan  |d 160000  |d 160100  |e 160000PW1082261246  |e 160100PW1082261246  |k 0/160000/  |k 1/160000/160100/  |p 1  |x j 
999 |a KXP-PPN1556004613  |e 2962768954 
BIB |a Y 
SER |a journal 
JSO |a {"note":["Gesehen am 28.03.2017"],"relHost":[{"disp":"The interference of selected cytotoxic alkaloids with the cytoskeleton an insight into their modes of actionMolecules","name":{"displayForm":["Molecular Diversity Preservation International"]},"recId":"311313132","part":{"year":"2016","issue":"7","text":"21(2016,7) Artikel-Nummer 906, 22 Seiten","extent":"22","pages":"906","volume":"21"},"id":{"issn":["1420-3049"],"zdb":["2008644-1"],"eki":["311313132"]},"origin":[{"dateIssuedDisp":"1996-","publisher":"MDPI","dateIssuedKey":"1996","publisherPlace":"Basel"}],"pubHistory":["1.1996 -"],"physDesc":[{"extent":"Online-Ressource"}],"language":["eng"],"type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 25.06.20"],"title":[{"title":"Molecules","subtitle":"a journal of synthetic chemistry and natural product chemistry","title_sort":"Molecules"}]}],"person":[{"display":"Wang, Xiaojuan","family":"Wang","role":"aut","given":"Xiaojuan"},{"role":"aut","given":"Mine","family":"Tanaka","display":"Tanaka, Mine"},{"family":"Krstin","role":"aut","given":"Sonja","display":"Krstin, Sonja"},{"family":"Peixoto","role":"aut","given":"Herbenya","display":"Peixoto, Herbenya"},{"display":"Wink, Michael","role":"aut","given":"Michael","family":"Wink"}],"title":[{"title_sort":"interference of selected cytotoxic alkaloids with the cytoskeleton","subtitle":"an insight into their modes of action","title":"The interference of selected cytotoxic alkaloids with the cytoskeleton"}],"physDesc":[{"extent":"22 S."}],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"doi":["10.3390/molecules21070906"],"eki":["1556004613"]},"origin":[{"dateIssuedDisp":"12 July 2016","dateIssuedKey":"2016"}],"name":{"displayForm":["Xiaojuan Wang, Mine Tanaka, Sonja Krstin, Herbenya Silva Peixoto and Michael Wink"]},"recId":"1556004613"} 
SRT |a WANGXIAOJUINTERFEREN1220