J 2023

The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties

TRAVNICEK, Zdenek, Jan VANCO, Jan BELZA, Jan HOSEK, Zdenek DVORAK et. al.

Basic information

Original name

The Gold(I) Complex with Plant Hormone Kinetin Shows Promising In Vitro Anticancer and PPARγ Properties

Authors

TRAVNICEK, Zdenek (203 Czech Republic), Jan VANCO (203 Czech Republic), Jan BELZA (203 Czech Republic), Jan HOSEK (203 Czech Republic), Zdenek DVORAK (203 Czech Republic), Rene LENOBEL (203 Czech Republic), Igor POPA (203 Czech Republic), Karel ŠMEJKAL (203 Czech Republic, belonging to the institution) and Pavel UHRIN (40 Austria)

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2023, 1661-6596

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.600 in 2022

RIV identification code

RIV/00216224:14160/23:00133785

Organization unit

Faculty of Pharmacy

UT WoS

000930771000001

Keywords in English

gold(I) complex; kinetin; anticancer; anti-inflammatory; in vitro; PPAR; cell cycle; apoptosis; ROS

Tags

Tags

International impact, Reviewed
Změněno: 4/4/2024 19:10, Mgr. Daniela Černá

Abstract

V originále

Motivated by the clinical success of gold(I) metallotherapeutic Auranofin in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh3)] complex (1), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex (1) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC50 approximate to 1-5 mu M, which was even significantly better than that for the conventional platinum-based drug Cisplatin while comparable with Auranofin. Although its ability to inhibit transcription factor NF-kappa B activity did not exceed the comparative drug Auranofin, it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPAR gamma), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex (1) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex (1) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects.

Links

GF21-38204L, research and development project
Name: Komplexy vybraných přechodných kovů s rostlinnými látkami s anti-NF-kappa B a pro-PPAR duální aktivitou
Investor: Czech Science Foundation, Partner Agency (Austria)