Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

Abstract

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

Anti-Photoaging and Anti-Melanogenesis Effects of Fucoidan Isolated from Hizikia fusiforme and Its Underlying Mechanisms

“…Cell death can occur through three routes: autophagy, necrosis, and apoptosis. Apoptosis is an intrinsic cellular suicidal mechanism, which is regulated by a complex network of signaling pathways, such as Caspase, Bax, Bcl-xL, and PARP pathway [ 41 , 42 , 43 , 44 ]. To further investigate the photoprotective mechanism of fucoidan, the apoptotic bodies and the expression of apoptosis-related proteins in UVB-irradiated HaCaT cells were measured.…”

Journey of anthraquinones as anticancer agents – a systematic review of recent literature

“…117 Perry et al synthesized a series of 1,4-and 2,6-di functionalized amido anthracene-9,10-diones and examined their cytotoxicity along with telomerase inhibitory activity. Among the synthesized, piperidine 2, 6-anthraquinone derivative (88) and N,N 0 -dimethiodide derivative (89) elicited good enzymatic inhibition of telomerase with IC 50 values of 4.5 and 9.4 mM, respectively. 118 Huang et al reported the synthesis of 1,5-bisthioanthraquinones and 1,5-bisacyloxyanthraquinones and examined their telomerase activity along with the expression of telomerase.…”

“…This reaction further sets off the e-cysteine protease pathway. 88 Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) models were used to analyze the structure–activity relationship of the compounds. From the studies, it was interpreted that the activity of the compounds greatly depended on the electron-withdrawing capacity of the nitro group at the C-1 position; the higher the electron-withdrawing capacity, the more the inhibitory activity of the compound.…”

Preventive Effects of Anthraquinones Isolated from an Endophytic Fungus, Colletotrichum sp. JS-0367 in Tumor Necrosis Factor-α-Stimulated Damage of Human Dermal Fibroblasts

“…It prevented the generation of ROS, intracellular calcium ion levels, and phosphorylation of MAPKs in glutamate-mediated apoptosis [ 38 ]. Moreover, many studies have reported that anthraquinones, as antioxidants, have the potential to suppress oxidative stress within cells [ 43 , 44 , 45 , 46 ]. Thus, we focused on suppressing the oxidative potential of these anthraquinones in HDFs.…”