The objective of our study is to highlight the therapeutic effect and mechanism of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich fraction exerts its anticancer activity on a human breast cancer cell line (T47D) and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH’s of six flaxseed cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed the most significant cytotoxic activity against ER-receptor positive breast cell lines MCF7 and T47D with IC50 13.8 and 15.8 µg/ml, respectively. Moreover, PFH-G9 reduced the expression of the metastasis marker, 1-α, metalloproteinases and vascular endothelial growth factor (VEGF), one of the most potent stimulators of angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO) or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites carcinoma (EAC) resulted in reducing the tumor volume, the expression of estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced expression of caspase-3.

A novel series of cyclic 2-oxindole derivatives incorporating 2-amino-tetrahydroquinolin-5-one were prepared. The structures of the prepared compounds were elucidated using different spectral tools. The regio-orientation of the reaction products was elucidated through NOE difference experiments and through using substituents on the ortho position to affect further cyclization. Antitumor and antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity. With respect to the antitumor activity, the compounds showed more potent cytotoxic effect only toward the human breast cancer cell line MCF-7. Also, we found that derivatives containing an ester group (8c, 11b, 14b, and 15b) are more active than those containing a cyanide group (8a, 11a, 14a, and 15a). Moreover, compounds 15b and 8b are the most active derivatives in this group. These two compounds showed apoptotic inhibition of the proliferation of human breast adenocarcinoma MCF-7 cells through DNA fragmentation, induction of the tumor suppressor protein p53, induction of caspase-9, and finally the inhibition of angiogenesis by decreasing vascular endothelial growth factor expression and secretion.

BackgroundTamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.MethodsAn in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.ResultsOur results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well.Conclusion3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in in vitro experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5′-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers in vivo by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.