Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer
Cells

J 2017

Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells

NEHYBOVÁ, Tereza; Jan ŠMARDA; Lukáš DANIEL; Marek STIBOREK; Viktor KANICKÝ et al.

Základní údaje

Originální název

Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells

Autoři

NEHYBOVÁ, Tereza; Jan ŠMARDA; Lukáš DANIEL; Marek STIBOREK ; Viktor KANICKÝ; Ivan SPASOJEVIČ; Jan PREISLER; Jiří DAMBORSKÝ a Petr BENEŠ

Vydání

International Journal of Molecular Sciences, Basel, MDPI, 2017, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/17:00094712

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

breast cancer; copper; proteasome; reactive oxygen species; wedelolactone

Štítky

NZ, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 4. 2018 08:45, Ing. Nicole Zrilić

Anotace

V originále

Wedelolactone is a multi-target natural plant coumestan exhibiting cytotoxicity towards cancer cells. Although several molecular targets of wedelolactone have been recognized, the molecular mechanism of its cytotoxicity has not yet been elucidated. In this study, we show that wedelolactone acts as an inhibitor of chymotrypsin-like, trypsin-like, and caspase-like activities of proteasome in breast cancer cells. The proteasome inhibitory effect of wedelolactone was documented by (i) reduced cleavage of fluorogenic proteasome substrates; (ii) accumulation of polyubiquitinated proteins and proteins with rapid turnover in tumor cells; and (iii) molecular docking of wedelolactone into the active sites of proteasome catalytic subunits. Inhibition of proteasome by wedelolactone was independent on its ability to induce reactive oxygen species production by redox cycling with copper ions, suggesting that wedelolactone acts as copper-independent proteasome inhibitor. We conclude that the cytotoxicity of wedelolactone to breast cancer cells is partially mediated by targeting proteasomal protein degradation pathway. Understanding the structural basis for inhibitory mode of wedelolactone might help to open up new avenues for design of novel compounds efficiently inhibiting cancer cells.

Návaznosti

GA15-05387S, projekt VaV

Název: Laserově desorpční hmotnostní spektrometrie pro analýzu molekul a nanočástic

Investor: Grantová agentura ČR, Laserově desorpční hmotnostní spektrometrie pro analýzu molekul a nanočástic

LO1214, projekt VaV

Název: Centrum pro výzkum toxických látek v prostředí (Akronym: RECETOX)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Centrum pro výzkum toxických látek v prostředí

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

MUNI/A/0967/2015, interní kód MU

Název: Podpora výzkumné činnosti studentů molekulární biologie a genetiky 4 (Akronym: MBG4)

Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů molekulární biologie a genetiky 4, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

NEHYBOVÁ, Tereza; Jan ŠMARDA; Lukáš DANIEL; Marek STIBOREK; Viktor KANICKÝ; Ivan SPASOJEVIČ; Jan PREISLER; Jiří DAMBORSKÝ a Petr BENEŠ. Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells. International Journal of Molecular Sciences. Basel: MDPI, 2017, roč. 18, č. 4, s. nestránkováno, 14 s. ISSN 1422-0067. Dostupné z: https://doi.org/10.3390/ijms18040729.

@article{1378197,
   author = {Nehybová, Tereza and Šmarda, Jan and Daniel, Lukáš and Stiborek, Marek and Kanický, Viktor and Spasojevič, Ivan and Preisler, Jan and Damborský, Jiří and Beneš, Petr},
   article_location = {Basel},
   article_number = {4},
   doi = {https://doi.org/10.3390/ijms18040729},
   keywords = {breast cancer; copper; proteasome; reactive oxygen species; wedelolactone},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells},
   url = {http://www.mdpi.com/1422-0067/18/4/729},
   volume = {18},
   year = {2017}
}

TY  - JOUR
ID  - 1378197
AU  - Nehybová, Tereza - Šmarda, Jan - Daniel, Lukáš - Stiborek, Marek - Kanický, Viktor - Spasojevič, Ivan - Preisler, Jan - Damborský, Jiří - Beneš, Petr
PY  - 2017
TI  - Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells
JF  - International Journal of Molecular Sciences
VL  - 18
IS  - 4
SP  - nestránkováno
EP  - nestránkováno
PB  - MDPI
SN  - 14220067
KW  - breast cancer
KW  - copper
KW  - proteasome
KW  - reactive oxygen species
KW  - wedelolactone
UR  - http://www.mdpi.com/1422-0067/18/4/729
L2  - http://www.mdpi.com/1422-0067/18/4/729
N2  - Wedelolactone is a multi-target natural plant coumestan exhibiting cytotoxicity towards cancer cells. Although several molecular targets of wedelolactone have been recognized, the molecular mechanism of its cytotoxicity has not yet been elucidated. In this study, we show that wedelolactone acts as an inhibitor of chymotrypsin-like, trypsin-like, and caspase-like activities of proteasome in breast cancer cells. The proteasome inhibitory effect of wedelolactone was documented by (i) reduced cleavage of fluorogenic proteasome substrates; (ii) accumulation of polyubiquitinated proteins and proteins with rapid turnover in tumor cells; and (iii) molecular docking of wedelolactone into the active sites of proteasome catalytic subunits. Inhibition of proteasome by wedelolactone was independent on its ability to induce reactive oxygen species production by redox cycling with copper ions, suggesting that wedelolactone acts as copper-independent proteasome inhibitor. We conclude that the cytotoxicity of wedelolactone to breast cancer cells is partially mediated by targeting proteasomal protein degradation pathway. Understanding the structural basis for inhibitory mode of wedelolactone might help to open up new avenues for design of novel compounds efficiently inhibiting cancer cells.
ER  -

NEHYBOVÁ, Tereza; Jan ŠMARDA; Lukáš DANIEL; Marek STIBOREK; Viktor KANICKÝ; Ivan SPASOJEVIČ; Jan PREISLER; Jiří DAMBORSKÝ a Petr BENEŠ. Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2017, roč.~18, č.~4, s.~nestránkováno, 14 s. ISSN~1422-0067. Dostupné z: https://doi.org/10.3390/ijms18040729.

Přehled o publikaci