Antimicrobial Peptides (AMPs) have unique anticancer properties, but their clinical application is currently limited by an inadequate margin of safety. A prodrug strategy associated with a combination therapy approach could address this limitation by increasing their therapeutic index and their efficacy. Accordingly, the first targeted anticancer polymeric prodrug candidates of AMPs, intended for combination therapy with another polymeric prodrug of an approved antineoplastic agent (doxorubicin), were synthesized as either a PEG-based dual-release prodrug or two individual pegylated prodrugs. The latter are based on a cathepsin B-labile peptide linker and an acid-sensitive acyl hydrazone bond for the AMP and doxorubicin prodrugs, respectively. Anticancer activities and toxicity differentials achieved with the free peptide and its polymer conjugates against ovarian, cancer and non-malignant, cells, indicate that protease-dependent reversible pegylation could be implemented to increase the therapeutic indices of AMPs in cancer therapy. The results obtained also show that this approach can be developed if the releasable PEG linker can be optimised to conciliate the attributes and restrictions of pegylation against proteases. In addition, combination of the polymeric prodrugs of the AMP and of doxorubicin provides additive antitumor effects which could be exploited to enhance the efficacy of the AMP candidate.

Aim: To investigate the cytotoxic effects of tamoxifen on the breast cancer cell line (MCF7). Methods:The cytotoxic effects of tamoxifen on MCF7 cells were investigated using caspase-9 activity and high content screening assays. Apoptosis mechanisms following tamoxifen treatment were also investigated. Results:The most significant cytotoxic effect of tamoxifen in MCF7 cells was a half-maximal inhibitory concentration (IC 50 ) of 4.506 µg/mL. A significant increase in caspase-9 activity was also observed when MCF7 cells were treated with tamoxifen (5 µg/mL). Furthermore, increased cell membrane permeability, cytochrome c level, and nuclear intensity were observed with tamoxifen (100 µg/mL) compared with doxorubicin (20 µg/mL) treatment. However, a noticeable decrease in cell viability and mitochondrial membrane permeability was observed with tamoxifen (100 µg/mL) treatment compared with doxorubicin (20 µg/mL) as a positive control. Conclusion:Tamoxifen showed in vitro cytotoxic effects in MCF7 cells as demonstrated by high-content screening and caspase-9 activity assays. Tamoxifen inhibits estrogen mechanisms, although toxic effect was observed.

Objectives:To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells.Methods:This is a prospective study. Anastrozole’s mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research’s, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016.Results:The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control.Conclusion:Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.