Cancer is known to be a fierce disease that causes a large percentage of the deaths worldwide. The common cancer treatments; chemotherapy, radiotherapy and surgery are known for their severe side effects; therefore scientists are working on finding solutions to reduce these drawbacks. One of these treatment systems is the sustained released drugs formulations, these systems depend on the encapsulation of the chemotherapy within an emulsifying agent, in order to obtain a slow drug release of low doses over long time intervals. In this study, the anti-cancer effects of free and encapsulated sinapic acid was tested against lung (A549), and colon (CaCo2) cancer cell lines, along with normal fibroblast cells (HFB4) as a negative control. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed for IC 50 evaluation, also cell cycle assay was performed to detect cell cycle arrest status and related anti-apoptotic and pro-apoptotic; Blc-2, BAX, and P53 gene profile fold changes post cellular treatment. Data recorded revealed that encapsulated SA showed a lower toxicity than the free form to both cell lines and also to the normal cells. The cell cycle analysis showed a cell cycle arrest at the G2/M phase post cell treatment with the free and encapsulated sinapic acid accompanied with up regulation of Bax and P53 and a down regulation of Blc-2 genes in both cell lines. The data suggest a promising anti-cancer and anti-proliferative potential of free and encapsulated sinapic acid. Also they show that the anti-cancer effect of free and encapsulated sinapic acid is quite close.

Introduction. The extremely-low frequency electromagnetic field (ELFEMF) has been proposed for use in cancer therapy since it was found that magnetic waves interfere with many biological processes. Gold nanoparticles (Au-NPs) have been widely used for drug delivery during cancer in vitro studies due to their low cytotoxity and high biocompatibility. The electroporation of cancer cells in a presence of Au-NPs (EP Au-NPs) can induce cell apoptosis, alterations of cell cycle profile and morphological changes. The impact of ELFEMF and EP Au-NPs on morphology, cell cycle and activation of apoptosis-associated genes on Hep-2 laryngeal cancer cell line has not been studied yet. Materials and methods. ELFEMF on Hep-2 cells were carried out using four different conditions: 25/50 mT at 15/30 min, while Au-NPs were used as direct contact (DC) or with electroporation (EP, 10 pulses at 200V, equal time intervals of 4 sec). MTT assay was used to check the toxicity of DC Au-NPs. Expression of CASP3, P53, BAX and BCL2 genes was quantified using qPCR. Cell cycle was analyzed by flow cytometry. Hematoxylin and eosin (HE) staining was used to observe cell morphology. Results. Calculated IC 50 of DC Au-NPs 24.36 µM (4.79 µg/ml) and such concentration was used for further DC and EP AuNPs experiments. The up-regulation of pro-apoptotic genes (CASP3, P53, BAX) and decreased expression of BCL2, respectively, was observed for all analyzed conditions with the highest differences for EP AuNPs and ELFEMF 50 mT/30 min in comparison to control cells. The highest content of cells arrested in G2/M phase was observed in ELFEMF-treated cells for 30 min both at 25 or 50 mT, while the cells treated with EP AuNPs or ELFEMF 50 mT/15 min showed highest ratios of apoptotic cells. HE staining of electroporated cells and cells exposed to ELFEMF's low and higher frequencies for different times showed nuclear pleomorphic 160 Mohammed A. Alshehri et al. ©Polish Society for Histochemistry and Cytochemistry Folia Histochem Cytobiol. 2019 10.5603/FHC.a2019.0018 www.fhc.viamedica.pl cells. Numerous apoptotic bodies were observed in the irregular cell membrane of neoplastic and necrotic cells with mixed euchromatin and heterochromatin. Conclusions. Our observations indicate that treatment of Hep-2 laryngeal cancer cells with ELFEMF for 30 min at 25-50 mT and EP Au-NPs can cause cell damage inducing apoptosis and cell cycle arrest.

The present work aimed to evaluate the reactivity of natural bioflavonoid hesperidin (HSP) and synthetically derived XAV939 (XAV) against human hepatocellular carcinoma (HepG2), human breast cancer (MDA-MB231) cancer cell lines, and related molecular and pathological profiles. Data recorded revealed that the cytotoxic potential of the tested products was found to be cell type-and concentration-dependent. The halfmaximal inhibitory concentration (IC 50 ) value of the HSP-XAV mixture against MDA-MB231 was significantly decreased in the case of using the HSP-XAV mixture against the HepG2 cell line. Also, there was a significant upregulation of the phosphotumor suppressor protein gene (P53) and proapoptotic genes such as B-cell lymphomaassociated X-protein (Bax, CK, and Caspase-3), while antiapoptotic gene B-cell lymphoma (Bcl-2) was significantly downregulated compared with the untreated cell control. The cell cycle analysis demonstrated that DNA accumulation was detected mainly during the G2/ M phase of the cell cycle accompanied with the elevated reactive oxygen species level in the treatment of HepG2 and MDA-MB231 cell lines by the HSP-XAV mixture, more significantly than that in the case of cell control. Finally, our finding suggests that both HSP and XAV939 and their mixture may offer an alternative in human liver and breast cancer therapy.