Toward understanding the antitumor effects of water-soluble fullerene derivatives on lung cancer cells: apoptosis or autophagy pathways?
Journal
Journal of Medicinal Chemistry
Journal Volume
62
Journal Issue
15
Pages
7111-7125
Date Issued
2019
Author(s)
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. ? 2019 American Chemical Society.
SDGs
Other Subjects
adenosine triphosphate; amino acid; antineoplastic agent; carbon; cisplatin; doxorubicin; fullerene derivative; glutathione; propidium iodide; thioacid; antineoplastic agent; fullerene derivative; water; A-549 cell line; acute toxicity; animal experiment; antineoplastic activity; apoptosis; aqueous solution; Article; autophagy; breathing; cell death; cell proliferation; chemical structure; controlled study; drug synthesis; endothelium cell; gel permeation chromatography; hydrodynamics; in vitro study; LD50; lung cancer; lung cancer cell line; mass spectrometry; mouse; nonhuman; nuclear magnetic resonance spectroscopy; oxygen consumption; tumor growth; zebra fish; animal; apoptosis; autophagy; cell survival; dose response; drug effect; drug screening; human; lung tumor; metabolism; physiology; procedures; solubility; treatment outcome; tumor cell line; A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Autophagy; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Fullerenes; Humans; Lung Neoplasms; Solubility; Treatment Outcome; Water; Xenograft Model Antitumor Assays; Zebrafish
Type
journal article