Differential cytotoxicity and sonosensitization by sanazole: effect of cell type and acoustic parameters

Abstract

Sanazole seems to be an efficient cytotoxic agent for the treatment of solid tumours and a promising sonosensitizer under aerobic conditions.

Evaluation of Sanazole Cytotoxicity in Human Drug-Sensitive and MDR Uterine Sarcoma Cells

“…elevation whereas the peroxides production was generally lower in comparison in both cell variants. This differential elevation in intracellular ROS might be dependent on cell type as shown in previous studies [17,18]. Also, the data shows that the resistant cells always possessed lower intracellular ROS levels, especially at higher doses, which might be due to the so-called adaptive antioxidant response [22].…”

“…Though the exact active products are not known, yet, the activation process has been attributed to xanthine oxidase and NADPH/cytochrome P450 reductase [15]. As implied, sanazole effect is attributed to its ability to mimic oxygen in being an electron affinic compound stably accommodating a one-electron, thus its efficacy might be more acknowledged in the absence of oxygen (hypoxic conditions), however, we have previously shown that it can be useful under normoxic conditions [16][17][18].…”

“…The analysis was performed with flow cytometry using hydroethidine (HE) and dichlorofluorescein diacetate (DCFH-DA) (Molecular Probes, Eugene, OR, USA) [18,22]. Cells were collected, washed twice with PBS, and resuspended in 2 μM HE or 5 μM DCFH-DA in PBS.…”

Ultrasound-Induced New Cellular Mechanism Involved in Drug Resistance

“…The stock solution was sterilized by filtration through a 0.22-µm filter and stored in aliquots at −20°C until use. In dual treatment protocols, Dox was added at a final concentration of 1 µM, the dose corresponding to the maximum apoptotic induction based on dose-dependent DNA fragmentation analysis (according to the method of Sellins and Cohen [18]). Two sets of protocols were carried out based on the time of application of each treatment; (a) simultaneous-treatment protocols , in which both Dox and US were applied simultaneously and DOX remained in the medium for 24 hr until measurements, (b) sequential-treatment protocols , in which either Dox or US was applied in the first day followed by the application of the other in the second day.…”

“…The impact of US hits on intracellular targets manifests as increased intracellular oxidative stress, induction of apoptosis [11], [12], [13], alteration in gene expression levels, and DNA damage [14], [15], [16]. Although these manifestations correlated with increased cell killing in many studies, reflecting the potential of US as an adjuvant tool in cancer eradication and further supporting the rationale of employing US in MDR reversal, there were occasions in which the enhancement of cell killing was not satisfactory, especially for solid tumor-derived (adherent) cancer cell lines [17], [18]. The decade-old studies on the use of US in MDR reversal showed in some cases higher sensitivity of drug-resistant cells to US exposure [8], [19], [20].…”