Artemisinins as potential anticancer agents: uptake detection in erythrocytes using Fourier transform infrared spectroscopy and cytotoxicity against bladder cancer cells

Abstract

Aims Semisynthetic derivatives of the antimalarial drug artemisinin may also possess anticancer properties. The ability to detect artemisinin uptake and distribution in cells would facilitate live cell imaging without labelling. This study describes mid-range infrared absorption spectra for three artemisinin variants and attempts to detect their presence in a simple cell model (erythrocytes). Cytotoxicity assays assess potential anticancer properties against bladder cancer cells. Methods Mid-range Fourier transform infrared spectra were obtained from dry preparations of dihydroartemisinin (DHA), artesunate (ART) and artemether (ARTE). Erythrocytes were prepared from normal blood and incubated for 30 min at 37°C with the three artemisinin derivatives. Cytospin preparations were prepared on aluminium foil for spectroscopy. Potential for growth inhibition in the RT112 bladder carcinoma cell line was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide residual viable biomass method. Results Spectra were obtained from the three native compounds. Repeat scans after 8 weeks showed ART and ARTE to be stable, stored under manufacturer's recommendations. DHA exhibited marked changes over the same period. It was possible by subtraction to detect DHA in cytospins, but not ART or ARTE. The fit between the subtraction spectrum and that of the native compound was >80%. DHA and ART showed strong cytotoxic potential against RT112 cells. Conclusions The artemisinin derivatives tested exhibit unique mid-range infrared absorption spectra which can be used to monitor degradation and, for DHA, can be detected by subtraction in loaded erythrocytes rendering future imaging studies feasible. Its cytotoxic efficacy against RT112 cells suggests bladder cancer as a possible target disease.

Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer

“…Ever since the discovery of the antineoplastic capabilities of artemisinin and its derivatives, research has been underway to assess the possibility of utilizing this compound and extrapolating it from the lab to the patient. To determine the efficiency of the drug against cancer cells, several clinical trials have been conducted with neoplastic cell cultures, animals, and humans [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Impact of processing methods on the dissolution of artemether from two non-ordered mesoporous silicas

“…Artemether (Fig.1) is a crystalline drug used as an antimalarial agent that kills malarial parasites by alkylating biomolecules through free radical formation (Meshnick, 2002). Artemether also has the potential to kill cancerous cells (Humphreys et al, 2016). Two grades of silica were employed in preparing formulations encompassing four different methods, namely physical mixing, co-grinding, solvent evaporation and lyophilised solid dispersions.…”

Dihydroartemisinin induces apoptosis in human bladder cancer cell lines through reactive oxygen species, mitochondrial membrane potential, and cytochrome C pathway

“…Here we indicated that DHA inhibited cell proliferation and induced apoptosis in a concentration-dependent manner in EJ-138 and HTB-9 cells [Figure 1a – c ]. Recently, some artemisinin derivatives showed potential anticancer effects on RT112 bladder cancer cells,[ 33 ] but there is no further information about molecular mechanisms of this cytotoxicity. Our recent results showed that DHA initiated intrinsic or mitochondrial-dependent apoptotic pathway.…”

“…in 2013 investigated some features of DHA in T24 bladder cancer cell lines. [ 23 ] However, in Jun et al . 's study, evaluation of cell viability, measurement of ROS and mitochondrial membrane potential (Δψ m ), and cytochrome c expression levels have not been performed.…”