Toward Understanding the Antitumor Effects of Water-Soluble Fullerene Derivatives on Lung Cancer Cells: Apoptosis or Autophagy Pathways?

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.

<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

“…Two different types of fullerene derivatives were found to be cytotoxic to A549: compounds with C−N (F1-F7) and C−S (F8-F10) linkages between the solubilizing functional addends and the fullerene cage. 41 However, IC 50 values were not determined in the previous work. As a matter of fact, even in the current study the IC 50 values of the ten compounds used for building QSAR model were obtained from testing a total of 22 fullerene derivatives, of which 12 compounds did not show IC 50 values after evaluation.…”

Progress in Antiviral Fullerene Research

“…Moreover, carboxylic acid derivatives of fullerenes can cut DNA under visible light irradiation, with the potential for use as photosensitive biochemical probes [ 34 ]. Fullerene C 60 carboxylic acid derivatives also exhibit neuroprotective activity [ 35 ] and strongly inhibit tumor growth in a zebrafish xenograft model [ 36 ]. Because nanoparticles have been approved as drugs and drug carriers, fullerenes have great potential as drugs or gene delivery carriers [ 37 , 38 ].…”

Reversible 1:1 Inclusion Complexes of C60 Derivatives in α- and β-Cyclodextrins: Implications for Molecular Recognition-Based Sensing and Supramolecular Assembly

“…[60]­Fullerenes (C 60 ) and their derivatives have attracted a lot of attention in recent years and have been successfully applied to materials science and biological technology. , However, the practicality of these potential biomedical applications of C 60 has been hampered, owing to their low solubility in water and other common solvents . Several approaches have been explored for preparing water-soluble fullerenes, for example, carboxylic acid fullerene derivatives , and fullerol. , On the other hand, as multifunctional molecular receptors, cyclodextrins (CDs) can selectively bind a wide variety of guest molecules through hydrophobic interactions to form host–guest inclusion complexes or nanometer supramolecular assemblies. − Nowadays, investigations on the molecular recognition and assembly or self-assembly of CDs and their derivatives are still one of the current interests in chemical and biological systems. The C 60 –CD related complex is a kind of functional compound which can combine the advantages of the CD structure and fullerene function.…”

“…1,2 However, the practicality of these potential biomedical applications of C 60 has been hampered, owing to their low solubility in water and other common solvents. 3 Several approaches have been explored for preparing water-soluble fullerenes, 4 for example, carboxylic acid fullerene derivatives 5,6 and fullerol. 7,8 On the other hand, as multifunctional molecular receptors, cyclodextrins (CDs) can selectively bind a wide variety of guest molecules through hydrophobic interactions to form host− guest inclusion complexes or nanometer supramolecular assemblies.…”