Antineoplastic activity of a novel ruthenium complex against human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells

Abstract

Novel metal complexes have received much attention recently because of their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternatives to the currently used platinum-based drugs for cancer therapy, with less toxicity and fewer side effects. The beneficial properties of Ru, which make it a highly promising therapeutic agent, include its variable oxidative states, low toxicity, and high selectivity for cancer cells. The present study evaluated the cytotoxic effects of a ruthenium complex, namely cis-[Ru(1,10phenanthroline) 2 (imidazole) 2 ] 2þ (RuC), on human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells and analyzed metabolic parameters. RuC reduced HepG2 and HeLa cell viability at all tested concentrations (10, 50, and 100 nmol/L) at 48 h of incubation, based on the MTT, Crystal violet, and neutral red assays. The proliferation capacity of HepG2 cells did not recover, whereas HeLa cell proliferation partially recovered after RuC treatment. RuC also inhibited all states of cell respiration and increased the levels of the metabolites pyruvate and lactate in both cell lines. The cytotoxicity of RuC was higher than cisplatin (positive control) in both lineages. These results indicate that RuC affects metabolic functions that are related to the energy provision and viability of HepG2 and HeLa cells and is a promising candidate for further investigations that utilize models of human cervical adenocarcinoma and mainly hepatocellular carcinoma.

Optimization of TopoIV Potency, ADMET Properties, and hERG Inhibition of 5-Amino-1,3-dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Identification of a Lead with In Vivo Efficacy against MRSA

“…Cytotoxicity was determined for THP-1, HepG2, and HeLa cells as previously described. , Compound 79 was tested from 128 to 0.0625 μg/mL, and IC 50 was determined from nonlinear regression analysis of inhibition curves.…”

“…(S)-1-(5-Amino-trans-1,3-dioxan-2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (75). To a solution of Boc-amine 74 (1.64 g, 3.87 mmol, 1.00 equiv) in DCM (30 mL) at 0 °C was added dropwise trifluoroacetic acid (7.75 mL, 101 mmol, 26.1 equiv), and the resulting mixture was allowed to warm slowly to room temperature and stirred for 2 additional hours.…”

“…1 H NMR (400 MHz, CDCl 3 , contaminated with ethyl acetate and small impurities) δ: 8.66 (s, 1H), 8.21 (d, J = 9.1 Hz, 1H), 7.86 (br s, 1H), 7.74 (app d, J = 0.9 Hz, 2H), 7.08 (d, J = 9.1 Hz, 1H), 4.72 (d, J = 3.9 Hz, 1H), 4.71−4.61 (m, 1H), 4.47 (t, J = 10.9 Hz, 1H), 4.45 (t, J = 10.9 Hz, 1H), 4.20−4.05 (m, 3H), 4.10 (s, 3H), 3.61−3.53 (m, 1H), 3.45 (dd, J = 12.8, 8.5 Hz, 1H), 1.36 (s, 9H). 13 (S)-1-(5-Amino-trans-1,3-dioxan-2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (75). To a solution of protected amine 94 (0.612 g, 1.2 mmol, 1.00 equiv) in ethyl acetate (15 mL) was added ethylenediamine (1.2 mL, 18.02 mmol, 15 equiv) at room temperature.…”

Identifying anal and cervical tumorigenesis-associated methylation signaling with machine learning methods

“…Therefore, it is reasonable for us to predict that such probe may be a biomarker for cervical carcinoma. The next biomarker is cg05713971 near an effective gene called HERPUD1 Antineoplastic activity has been shown to be associated with gene HERPUD1 and further related to human cervical carcinoma according to a recent in vitro experiment ( 52 ). Such gene has also been detected to be regulated by functional microRNA miR-375 and further contributes to HPV-positive cervical cancer, validating our prediction ( 53 ).…”

Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes

“…The formation of G-quadruplex prevented telomerase from distinguishing telomere DNA primers to inhibit the expression of telomerase activity. Ruthenium (II) complex II44 , coordinated with diimidazole and polypyridine, could transform telomere into G-quadruplex and, thereby, effectively inhibit the proliferation of HeLa cervical, A549 lung, and HepG2 liver cancer cell lines, providing a broad spectrum of anticancer activity [ 142 , 143 ].…”