Toward understanding the antitumor effects of water-soluble fullerene derivatives on lung cancer cells: apoptosis or autophagy pathways?

Chui Wei Wong, Alexander V. Zhilenkov, Olga A. Kraevaya, Denis V. Mischenko, Pavel A. Troshin, Shan Hui Hsu

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Here we report the synthesis and investigation of anticancer effects of a series of water-soluble fullerene derivatives bearing amino acid (F1-F7) and thioacid (F8-F10) residues. Compounds F4 and F10 efficiently inhibited proliferation of lung cancer cells in vitro while being nontoxic to endothelial cells. It was revealed that the cancer cell death was caused by either autophagy (F4) or apoptosis (F10). Both fullerene derivatives strongly inhibited the tumor growth in the zebrafish xenograft model. In contrast to the vast majority of known cytostatics, fullerene derivatives do not show any significant acute toxicity effects in mice. Importantly, functional groups attached to the carbon cage affect interaction of the compounds with cancer cells, thus enabling realization of two different cell death mechanisms. The obtained results pave a way to the development of a new generation of selective antitumor drugs suppressing efficiently the proliferation of cancer cells while being nontoxic to normal cells.

Original languageEnglish
Pages (from-to)7111-7125
Number of pages15
JournalJournal of Medicinal Chemistry
Volume62
Issue number15
DOIs
Publication statusPublished - 8 Aug 2019

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