Oxidative stress plays an important role in zoledronic acid-induced autophagy

Title:

Oxidative stress plays an important role in zoledronic acid-induced autophagy

Creator:

Khandelwal, V. K. M., Mitrofan, L. M., Hyttinen, J. M. T., Chaudhari, K. R., Buccione, R., Kaarniranta, K., Ravingerová, T., and Mönkkönen, J.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:dd6a6930-7fe7-4e07-94ec-e50b1c4c5b65
uuid:dd6a6930-7fe7-4e07-94ec-e50b1c4c5b65
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, oxidační stres, oxidative stress, dendra2, GGOH, FOH, LC3B, prenylation, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Several pre-clinical and clinical studies have demonstrated zoledronic acid (Zol), which regulates the mevalonate pathway, has efficient anti-cancer effects. Zol can also induce autophagy. The aim of this study is to add new understanding to the mechanism of autophagy induction by Zol. LC3B-II, the marker for autophagy was increased by Zol treatment in breast cancer cells. Autophagosomes induced by Zol were visualized and quantified in both transient (pDendra2-hLC3) and stable MCF-7- GFP-LC3 cell lines. Acidic vesicular organelles were quantified using acridine orange. Zol induced a dose and time dependent autophagy. Treatment of Zol increased oxidative stress in MCF-7 cells, which was reversed by GGOH or anti-oxidants. On the other hand, treatment with GGOH or anti-oxidants resulted in decreased levels of LC3B-II. Further, the induced autophagy was irreversible, as the washout of Zol after 2 h or 24 h resulted in similar levels of autophagy, as induced by continuous treatment after 72 h. Thus, it can be summarized that Zol can induce a dose dependent but irreversible autophagy, by its effect on the mevalonate pathway and oxidative stress. This study adds to the understanding of the mechanism of action of Zol, and that it can induce autophagy at clinically relevant shorter exposure times in cancer cells., V. K. M. Khandelwal, L. M. Mitrofan, J. M. T. Hyttinen, K. R. Chaudhari, R. Buccione, K. Kaarniranta, T. Ravingerová, J. Mönkkönen., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2014 Volume:63 | Number:Suppl 4

Harvested from:

CDK

Metadata only:

false