In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives

Abstract

Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC50-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (4) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

“…After treatment with EM and Chr, a considerable reduction in the number of cancer cells was seen, as shown by the fact that the number of DAPI-stained cells was much lower in the Chr and EM-treated cells (Figure 18B,C), in comparison to the untreated control cells (Figure 18A). The in vitro anticancer properties of anthraquinone derivatives against four distinct cell lines: PC3, HT-29, HeLa, and HepG2 were reported [19]. All of the aforementioned studies allow us to hypothesize the tumor inhibitory effects of Chr and EM on HCT-116 and HeLa cell lines.…”

“…In recent years, there has been a great deal of interest in the synthesis of anthraquinone derivatives, as well as in the modification of their structures and the evaluation of their bioactivity. EM and Chr are the most important anthraquinone analogues [19]. In drug development, anthraquinones have become an important family of chemicals due to their wide range of biological characteristics.…”

Comparison of Balanites aegyptiaca parts: metabolome providing insights into plant health benefits and valorization purposes as analyzed using multiplex GC-MS, LC-MS, NMR-based metabolomics, and molecular networking

“…PC-3 cells were cultured under standard growth conditions (37 °C and 5% CO 2 in a humidified atmosphere) in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated FCS and 2 mM l -glutamine, while for HCT-116 McCoy's 5A medium supplemented with 10% (v/v) heat-inactivated FCS and 2 mM l -glutamine was used. 21 Cells were monitored daily using light microscopy and were passed whenever the confluency reached 90%. For passaging, the adherent cells were detached with 0.05% trypsin–EDTA for 3 min at 37 °C.…”

Seasonal and taxa impact on edible sea cucumber's metabolome and in relation to its cytotoxicity as analyzed via UHPLC/HR‐MS/MS‐based molecular networking and chemometrics

“…McCoy's 5A, phosphate-buffered saline (PBS), 0.05%trypsin-EDTA, and FCS, were purchased from Capricorn Scientific. PC-3 and HCT 116 cells were cultured and monitored under the exact conditions reported by Morgan et al (2022). Cells were monitored daily using light microscopy (LED lab binocular microscope, AmScope) and were passaged whenever the confluency reached 90%.…”