Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel

Ana Podolski-Renić, Sz. Bősze, Jelena Dinić, László Kocsis, F. Hudecz, Anta Csámpai, Milica Pešić

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7)-synthesized using improved methods providing controlled diastereoselectivity-in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.

Original languageEnglish
Pages (from-to)1132-1141
Number of pages10
JournalMetallomics
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Cinchona
Chalcone
Paclitaxel
Oxidants
Quinidine
Reactive Oxygen Species
Cells
Cell Line
Quinine
Neoplasms
Autophagy
P-Glycoprotein
Glioblastoma
Non-Small Cell Lung Carcinoma
Antineoplastic Agents
Glycoproteins
Colorectal Neoplasms
Cell Death
Cell death
Metals

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel. / Podolski-Renić, Ana; Bősze, Sz.; Dinić, Jelena; Kocsis, László; Hudecz, F.; Csámpai, Anta; Pešić, Milica.

In: Metallomics, Vol. 9, No. 8, 01.08.2017, p. 1132-1141.

Research output: Contribution to journalArticle

Podolski-Renić, Ana ; Bősze, Sz. ; Dinić, Jelena ; Kocsis, László ; Hudecz, F. ; Csámpai, Anta ; Pešić, Milica. / Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel. In: Metallomics. 2017 ; Vol. 9, No. 8. pp. 1132-1141.
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